Mutations in TAC1B : a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris
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Abstract
Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris .
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TL;DR
Mutations in TAC1B, a homolog of Candida albicans TAC1, are a novel determinant of clinical fluconazole resistance in Candida auris. In vitro evolution and Cas9 editing show TAC1B mutations increase fluconazole MIC and are prevalent among global fluconazole-resistant isolates.
Key findings
- In vitro evolution of fluconazole-susceptible AR0387 produced isogenic strains with fluconazole MICs of 8–64 mg/liter (parental MIC, 1 mg/liter); all five evolved strains had TAC1B mutations (R495G or F214S), no ERG11 or ERG3 mutations, and 3.3–5.4-fold higher CDR1 expression.
- Among 304 global C. auris isolates, 165 (54%) had TAC1B mutations; 148 of 294 isolates with susceptibility data (50%) were fluconazole resistant (MIC ≥32 mg/liter) and TAC1B-mutant, and 90% of TAC1B-mutant isolates were resistant. A640V was the most common TAC1B mutation (57 clade I isolates from 7 countries), always co-occurred with ERG11 K143R, and 98.2% of A640V+K143R isolates showed high-level resistance (>64 mg/liter).
- Cas9-RNP introduction of TAC1B A640V into AR0387 increased fluconazole MIC 8-fold; correcting A640V in AR0390 decreased MIC 16-fold.
- Under 16 mg/liter fluconazole, AR0387 accumulated lanosterol (46.0% ± 7.4%), 14-methyl-fecosterol (21.3% ± 4.8%), and the toxic sterol 14-methyl-ergosta-8,24(28)-dienol-3,6-diol (3.8% ± 1.9%), while evolved strains lacked the toxic sterol; [3H]fluconazole uptake was ~50% lower in 4 of 5 evolved strains (FLU-C2 did not differ significantly, P = 0.2842).
Methods
- In vitro evolution: AR0387 was grown in YPD with 8 or 32 mg/liter fluconazole, plated on RPMI with the same drug, and colonies were selected as FLU-A, FLU-B, FLU-C, plus second-passage FLU-A2 and FLU-C2; MICs were determined by modified CLSI broth microdilution.
- Molecular and physiological assays: sequencing of ERG11, ERG3, TAC1A, TAC1B, and UPC2; GC-MS sterol profiling; [3H]fluconazole uptake after glucose starvation; RT-qPCR for ERG11/CDR1/MDR1 and qPCR for copy number variation; Cas9-RNP transformations with the SAT-FLP system.
- Genomic survey: whole-genome sequencing data for 304 globally distributed C. auris isolates from four clades, variant calling with GATK, and fluconazole susceptibility testing for 294 isolates using a resistance threshold of ≥32 mg/liter.
Limitations
- Stated: in vitro evolution used a single genetic background and only fluconazole, so it is unknown whether other C. auris isolates or other triazoles would select different resistance mechanisms; further characterization of the C. auris TAC1B regulon is needed to understand similarities and differences with other Candida species.
- Stated/evident: roles of the UPC2 mutation and altered fluconazole uptake remain speculative, and the paper calls for further investigation of TAC1B/UPC2 effects on uptake and sterol profiles.
- Evident: functional validation focused on A640V; F214S and R495G were identified in evolved strains and clinical isolates but were not individually edited or complemented in this study, and many global TAC1B variants are associations rather than direct causality tests.
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- Findingown data
All fluconazole-evolved strains had wild-type ERG11 sequences matching that of parental AR0387.
“all evolved strains were found to have wild-type ERG11 sequences matching that of the parental AR0387.”
Quote in the paperSubstantial claim - Findingown data
Following growth in RPMI media without fluconazole, all fluconazole-evolved strains and parental AR0387 had largely similar sterol profiles.
“Following growth in RPMI media without fluconazole, all of the fluconazole-evolved strains and the parental AR0387 were observed to have largely similar sterol profiles”
Quote in the paperSubstantial claim - Findingown data
The five fluconazole-evolved Candida auris strains had fluconazole MICs ranging from 8 to 64 mg/liter.
“the five fluconazole-evolved strains were found to have MICs ranging from 8 to 64 mg/liter”
Quote in the paperSubstantial claim - Findingown data
Following growth in RPMI media supplemented with fluconazole, the sterol profiles of each fluconazole-evolved strain were dramatically different from that of AR0387.
“Following growth in RPMI media supplemented with fluconazole, the sterol profiles of each of the fluconazole-evolved strains were dramatically different from that of AR0387”
Quote in the paperSubstantial claim - Findingown data
Second-generation evolved strains FLU-A2 and FLU-C2 exhibited a further 2-to-4-fold increase in fluconazole MIC relative to the corresponding first-generation strains.
“Each of the second-generation evolved strains, FLU-A2 and FLU-C2, exhibited a further 2-to-4-fold increase in fluconazole MIC relative to the corresponding first-generation strains.”
Quote in the paperNot a substantial claim
- Findingown data
In AR0387 grown with fluconazole, lanosterol (46.0% ± 7.4%) and 14-methyl-fecosterol (21.3% ± 4.8%) were the two most prevalent sterols.
“lanosterol (46.0% ± 7.4%) and 14-methyl-fecosterol (21.3% ± 4.8%) were observed to be the two most prevalent sterols in AR0387.”
Quote in the paperSubstantial claim - Findingown data
AR0387 exhibited a fluconazole MIC of 1 mg/liter.
“AR0387 exhibited a fluconazole MIC of 1 mg/liter”
Quote in the paperNot a substantial claim - Findingown data
TAC1B mutations appear specific to a subset of Candida auris lineages or clades.
“and appear specific to a subset of lineages or clades”
Quote in the paperNot a substantial claim - Findingown data
A collection of isogenic Candida auris strains with increased fluconazole resistance was created via in vitro evolution from the fluconazole-susceptible clinical isolate AR0387.
“a collection of isogenic strains with increased fluconazole resistance was created via in vitro evolution utilizing the previously described fluconazole-susceptible C. auris clinical isolate AR0387”
Quote in the paperSubstantial claim - Findingown data
A multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant Candida auris isolates from a global collection.
“a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection”
Quote in the paperSubstantial claim - Findingown data
Mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole.
“These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole”
Quote in the paperSubstantial claim - Findingown data
Fluconazole MICs for all fluconazole-evolved strains were stable following storage at -80°C and multiple passages on fluconazole-free media.
“Fluconazole MICs for all fluconazole-evolved strains were observed to be stable following storage at –80°C and multiple passages on fluconazole-free media.”
Quote in the paperNot a substantial claim - Findingown data
No alteration in the copy number of ERG11, CDR1, or MDR1 was observed among the fluconazole-evolved strains.
“While no alteration in the copy number of ERG11, CDR1, or MDR1 was observed”
Quote in the paperSubstantial claim - Findingown data
A single mutation encoding A640V was found among 57 clinical isolates of C. auris from clade I.
“a single mutation (encoding A640V) which was found among 57 clinical isolates of C. auris from clade I”
Quote in the paperSubstantial claim - Findingown data
[3H]fluconazole accumulation was reduced by approximately 50% in FLU-A, FLU-B, FLU-C, and FLU-A2 relative to AR0387.
“[3H]fluconazole accumulation was observed to be reduced by approximately 50% in four of the fluconazole-evolved strains (FLU-A, FLU-B, FLU-C, and FLU-A2) relative to than that observed in AR0387”
Quote in the paperSubstantial claim - Findingcitation
Interrogation of whole-genome sequencing data for 304 globally distributed Candida auris isolates representing four major clades revealed 14 nonsynonymous TAC1B mutations and one deletion.
“Interrogation of a data set consisting of whole-genome sequencing data for 304 globally distributed C. auris isolates representing each of the four major clades revealed 14 nonsynonymous TAC1B mutations and one deletion”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Chow NA, Muñoz JF, Gade L, Berkow E, Li X, Welsh RM, Forsberg K, Lockhart SR, Adam R, Alanio A, Alastruey-Izquierdo A, Althawadi S, Belén Araúz A, Ben-Ami R, Bharat A, Calvo B, Desnos-Ollivier M, Escandón P, Gardam D, Gunturu R, Heath CH, Kurzai O, Martin R, Litvintseva AP, Cuomo CA 2020 Tracing the evolutionary history and global expansion of Candida auris using population genomic analyses. bioRxiv doi: 10.1101/2020.01.06.896548. PMC7188998 32345637 source
Not checked in the free run.
- Findingown data
No mutation in Candida auris ERG3 was observed in any fluconazole-evolved strain.
“no mutation in C. auris ERG3 was observed in any of the fluconazole-evolved strains.”
Quote in the paperSubstantial claim - Findingown data
Six resistant clade I isolates harbored two TAC1B mutations (A15T and S195C).
“six resistant isolates from clade I which harbored two TAC1B mutations (A15T and S195C)”
Quote in the paperSubstantial claim - Findingown data
Among the fluconazole-evolved strains, [3H]fluconazole uptake was decreased in 4 of the 5 strains compared to AR0387.
“this analysis revealed an intriguing decrease in [3H]fluconazole uptake in 4 of the 5 strains compared to AR0387”
Quote in the paperNot a substantial claim - Findingown data
Subtle variations in ERG11 and MDR1 expression, not exceeding 2.1-fold higher than AR0387, were observed among individual fluconazole-evolved strains.
“subtle variations in the levels of expression of the ERG11 and MDR1 genes, not exceeding 2.1-fold higher than the levels seen with AR0387, were also observed among individual fluconazole-evolved strains.”
Quote in the paperNot a substantial claim - Findingown data
Nearly all (98.2%) isolates with A640V and K143R mutations displayed high-level fluconazole resistance (>64 mg/liter).
“Nearly all (98.2%) of the isolates with A640V and K143R mutations displayed high-level fluconazole resistance (>64 mg/liter).”
Quote in the paperSubstantial claim - Findingown data
14-methyl-ergosta-8,24(28)-diene-3,6-diol was uniquely found in AR0387 (4% of total sterols) under fluconazole treatment.
“14-methyl-ergosta-8,24(28)-diene-3,6-diol, a sterol proposed to be toxic and important for the antifungal activity of the triazoles, was uniquely found in AR0387 (4% of total sterols)”
Quote in the paperNot a substantial claim - Findingown data
Mutations in TAC1B were identified among 165 (54%) of the 304 Candida auris isolates.
“In total, mutations in TAC1B were identified among 165 (54%) isolates.”
Quote in the paperSubstantial claim - Findingown data
The A640V mutation in TAC1B is the most common mutation found among fluconazole-resistant clinical isolates of C. auris.
“the mutation in TAC1B encoding the A640V amino acid substitution, the most common mutation found among fluconazole-resistant clinical isolates of C. auris”
Quote in the paperNot a substantial claim - Findingown data
There was no difference in [3H]fluconazole accumulation between AR0387 and AR0387_Δcdr1 (6,560 and 6,813 cpm; P = 0.9976).
“there was no difference in [3H]fluconazole accumulation between AR0387 and AR0387_Δcdr1 (6,560 and 6,813 cpm, respectively; P = 0.9976)”
Quote in the paperSubstantial claim - Findingown data
The A640V mutation alone is sufficient to elevate fluconazole resistance by 8-fold.
“Cas9-RNP-mediated genetic manipulations demonstrated that the mutation in TAC1B encoding the A640V amino acid substitution, the most common mutation found among fluconazole-resistant clinical isolates of C. auris, was sufficient alone to elevate fluconazole resistance by 8-fold.”
Quote in the paperSubstantial claim - Findingown data
Introduction of the wild-type TAC1B allele into AR0390, which harbors the A640V mutation, caused a 16-fold decrease in fluconazole MIC.
“when the same methods were used to introduce the wild-type TAC1B allele to isolate AR0390 (which harbors the TAC1B mutation encoding A640V), a 16-fold decrease in fluconazole MIC was observed”
Quote in the paperSubstantial claim - Findingown data
FLU-B, FLU-C, and FLU-C2 possess a TAC1B mutation encoding F214S.
“the FLU-B, FLU-C, and FLU-C2 strains were found to possess a mutation encoding the amino acid substitution F214S.”
Quote in the paperSubstantial claim - Findingown data
All five fluconazole-evolved strains had mutations encoding amino acid substitutions in TAC1B.
“all five fluconazole-evolved strains were found to have mutations encoding amino acid substitutions in TAC1B”
Quote in the paperSubstantial claim - Findingown data
A total of 14 nonsynonymous TAC1B mutations and one deletion were identified in the global collection.
“A total of 14 nonsynonymous TAC1B mutations and one deletion were identified”
Quote in the paperNot a substantial claim - Findingown data
FLU-A and its second-generation derivative FLU-A2 harbor a TAC1B mutation encoding R495G.
“Both the FLU-A strain and the corresponding second-generation derivative FLU-A2 were found to harbor a mutation encoding the amino acid substitution R495G”
Quote in the paperSubstantial claim - Findingown data
No mutations in C. auris ERG11 were identified among the fluconazole-evolved strains created in this study.
“no mutations in C. auris ERG11 were identified among the fluconazole-evolved strains created in this study”
Quote in the paperSubstantial claim - Findingcitation
The degree of CDR1 overexpression observed among fluconazole-evolved strains was similar to that previously reported among fluconazole-resistant clinical C. auris isolates.
“the degree of CDR1 overexpression observed among fluconazole-evolved strains was similar to that previously reported among fluconazole-resistant clinical C. auris isolates (20)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Rybak JM, Doorley LA, Nishimoto AT, Barker KS, Palmer GE, Rogers PD 27 3 2019, posting date Abrogation of triazole resistance upon deletion of CDR1 in a clinical isolate of Candida auris. Antimicrob Agents Chemother doi: 10.1128/AAC.00057-19. PMC6437491 30718246 source
Not checked in the free run.
- Findingown data
Introduction of the TAC1B A640V allele into the native TAC1B locus increased fluconazole MIC 8-fold relative to parental AR0387.
“Introduction of the TAC1BA640V allele into the native TAC1B locus was observed to increase the fluconazole MIC 8-fold relative to the parental AR0387”
Quote in the paperSubstantial claim - Findingown data
No mutations were identified in TAC1A or MRR1 among the fluconazole-evolved strains.
“While no mutations were identified in TAC1A or MRR1”
Quote in the paperSubstantial claim - Findingown data
50% (148) of the isolates with available susceptibility data were fluconazole resistant (MIC ≥32 mg/liter) and possessed a mutation in TAC1B.
“50% (148) of the isolates in this collection with available susceptibility data were found to be fluconazole resistant (MIC of ≥32mg/liter) and to possess a mutation in TAC1B.”
Quote in the paperSubstantial claim - Findingown data
Two of the three first-generation evolved strains, FLU-B and FLU-C, acquired the same TAC1B mutation (F214S) after selection following exposure to different concentrations of fluconazole (8 and 32 mg/liter, respectively).
“two of the three first-generation evolved strains, FLU-B and FLU-C, were found to have acquired the same TAC1B mutation (F214S) even after selection following exposure to different concentrations of fluconazole (8 and 32 mg/liter, respectively)”
Quote in the paperNot a substantial claim - Findingown data
F214S was found in 2 isolates from clade II and 1 isolate from clade IV.
“the F214S change was found in 2 isolates from clade II and in 1 isolate from clade IV”
Quote in the paperSubstantial claim - Findingown data
A sole UPC2 mutation encoding M365I was identified in FLU-C2.
“a sole mutation in UPC2 encoding the amino acid substitution M365I was identified in FLU-C2”
Quote in the paperNot a substantial claim - Findingown data
AR0387 had a large amount of 14-methyl-fecosterol (21%) under fluconazole treatment.
“in conjunction with a large amount of 14-methyl-fecosterol (21%), the direct precursor of this speculated toxic sterol”
Quote in the paperSubstantial claim - Findingown data
[3H]fluconazole accumulation in FLU-C2 did not significantly differ from that in AR0387 (5,438 versus 6,560 cpm; P = 0.2842).
“accumulation in FLU-C2 did not significantly differ from that in AR0387 (5,438 versus 6,560 cpm, respectively; P = 0.2842)”
Quote in the paperNot a substantial claim - Findingown data
In a global collection of over 300 C. auris clinical isolates, the majority (54%) have mutations in TAC1B.
“Among the members of this global collection, the majority (54%) of the isolates were found to have mutations in TAC1B”
Quote in the paperSubstantial claim - Findingown data
Three novel TAC1B mutations were observed in clade IV isolates lacking resistance-associated ERG11 mutations: K247E (n = 5), M653V (n = 7), and A651T (n = 16).
“we observed three novel TAC1B mutations in clade IV isolates lacking resistance-associated mutations in ERG11, including K247E (n = 5), M653V (n = 7), and A651T (n = 16)”
Quote in the paperSubstantial claim - Findingown data
Following growth in RPMI media supplemented with 16 mg/liter fluconazole, lanosterol predominated the total cellular sterols in the parental AR0387 isolate (46%).
“lanosterol predominated the total cellular sterols in the parental AR0387 isolate (46%)”
Quote in the paperSubstantial claim - Findingown data
All five fluconazole-evolved strains harbor one of two mutations in TAC1B (encoding F214S and R495G).
“all five strains were found to harbor one of two mutations in TAC1B (encoding F214S and R495G)”
Quote in the paperSubstantial claim - Findingown data
The mutations identified in fluconazole-evolved strains were included among the clinical TAC1B mutations.
“this included both of the mutations identified in fluconazole-evolved strains”
Quote in the paperSubstantial claim - Findingown data
All strains except FLU-C2 accumulated approximately 50% less [3H]fluconazole under energy-depleted conditions.
“All strains except for FLU-C2 were found to accumulate approximately 50% less [3H]fluconazole under energy-depleted conditions”
Quote in the paperNot a substantial claim - Findingown data
Following growth in RPMI media without fluconazole supplementation, the only notable difference in sterol levels among the fluconazole-evolved strains and AR0387 was a lack of detectable lanosterol in FLU-C2.
“Following growth in RPMI media without fluconazole supplementation, the only notable difference in levels of sterols among the fluconazole-evolved strains and AR0387 was a lack of detectable lanosterol, the substrate of ERG11, in the second-generation evolved FLU-C2 strain.”
Quote in the paperNot a substantial claim - Findingown data
CDR1 expression was significantly 3-to-5-fold higher in all five fluconazole-evolved strains than in AR0387 (P < 0.0001 for all evolved strains compared to AR0387).
“The level of expression of CDR1 was found to be significantly (3-to-5-fold) higher in all five fluconazole-evolved strains than in AR0387 (P < 0.0001 for all evolved strains compared to AR0387)”
Quote in the paperSubstantial claim - Findingown data
90% of all isolates with TAC1B mutations were resistant to fluconazole.
“90% of all isolates with TAC1B mutations were resistant to fluconazole”
Quote in the paperSubstantial claim - Findingown data
Each of the five TAC1B mutant strains exhibited elevated expression of CDR1.
“each of the five TAC1B mutant strains exhibited elevated expression of the ABC-type efflux pump-encoding gene CDR1”
Quote in the paperSubstantial claim - Findingown data
R495G was found in a single clade I Candida auris isolate.
“R495G was found in a single clade I isolate”
Quote in the paperNot a substantial claim - Findingown data
The two TAC1B mutations that arose during in vitro drug selection were present among fluconazole-resistant clinical Candida auris isolates.
“the two TAC1B mutations that arose during in vitro drug selection were found to be present among fluconazole-resistant clinical C. auris isolates”
Quote in the paperSubstantial claim - Findingown data
Following growth in RPMI media supplemented with 16 mg/liter fluconazole, ergosterol remained the principal sterol in all fluconazole-evolved strains, comprising more than 50% of sterols.
“Whereas ergosterol remained the principal sterol present in all fluconazole-evolved strains (comprising more than 50% of sterols)”
Quote in the paperSubstantial claim - Premisecitation
Fluconazole-resistant Candida auris isolates with no mutation in ERG11 have been described.
“as have fluconazole-resistant isolates of C. auris with no mutation in ERG11”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, Tarai B, Singh A, Upadhyaya G, Upadhyay S, Yadav P, Singh PK, Khillan V, Sachdeva N, Perlin DS, Meis JF 2018 A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother 73: 891– 899. doi: 10.1093/jac/dkx480. 29325167 source
Not checked in the free run.
- cites [14] Escandon P, Chow NA, Caceres DH, Gade L, Berkow EL, Armstrong P, Rivera S, Misas E, Duarte C, Moulton-Meissner H, Welsh RM, Parra C, Pescador LA, Villalobos N, Salcedo S, Berrio I, Varon C, Espinosa-Bode A, Lockhart SR, Jackson BR, Litvintseva AP, Beltran M, Chiller TM 2019 Molecular epidemiology of Candida auris in Colombia reveals a highly related, countrywide colonization with regional patterns in amphotericin B resistance. Clin Infect Dis 68: 15– 21. doi: 10.1093/cid/ciy411. 29788045 source
Not checked in the free run.
- Interpretationcitation
There are yet-to-be-identified mechanisms of fluconazole resistance in Candida auris.
“suggesting the presence of yet-to-be-identified mechanisms of fluconazole resistance (8, 14).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, Tarai B, Singh A, Upadhyaya G, Upadhyay S, Yadav P, Singh PK, Khillan V, Sachdeva N, Perlin DS, Meis JF 2018 A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother 73: 891– 899. doi: 10.1093/jac/dkx480. 29325167 source
Not checked in the free run.
- cites [14] Escandon P, Chow NA, Caceres DH, Gade L, Berkow EL, Armstrong P, Rivera S, Misas E, Duarte C, Moulton-Meissner H, Welsh RM, Parra C, Pescador LA, Villalobos N, Salcedo S, Berrio I, Varon C, Espinosa-Bode A, Lockhart SR, Jackson BR, Litvintseva AP, Beltran M, Chiller TM 2019 Molecular epidemiology of Candida auris in Colombia reveals a highly related, countrywide colonization with regional patterns in amphotericin B resistance. Clin Infect Dis 68: 15– 21. doi: 10.1093/cid/ciy411. 29788045 source
Not checked in the free run.
- Premisecitation
Triazole-resistant Candida auris isolates exhibit efflux pump activity up to 14-fold higher than that of Candida glabrata.
“triazole-resistant isolates of C. auris have been observed to exhibit efflux pump activity greatly exceeding (up to 14-fold higher) that of C. glabrata (17–19).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [17] Ben-Ami R, Berman J, Novikov A, Bash E, Shachor-Meyouhas Y, Zakin S, Maor Y, Tarabia J, Schechner V, Adler A, Finn T 13 1 2017, posting date Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel. Emerg Infect Dis doi: 10.3201/eid2302.161486. PMC5324804 28098529 source
Not checked in the free run.
- cites [18] Munoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CA 2018 Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun 9: 5346. doi: 10.1038/s41467-018-07779-6. 30559369 PMC6297351 source
Not checked in the free run.
- cites [19] Wasi M, Khandelwal NK, Moorhouse AJ, Nair R, Vishwakarma P, Bravo Ruiz G, Ross ZK, Lorenz A, Rudramurthy SM, Chakrabarti A, Lynn AM, Mondal AK, Gow NAR, Prasad R 2019 ABC transporter genes show upregulated expression in drug-resistant clinical isolates of Candida auris: a genome-wide characterization of ATP-binding cassette (ABC) transporter genes. Front Microbiol 10: 1445. doi: 10.3389/fmicb.2019.01445. 31379756 PMC6647914 source
Not checked in the free run.
- Premisecitation
Clinical isolates harboring the same ERG11 mutations and exhibiting a fluconazole MIC as low as 1 mg/liter have been described.
“clinical isolates harboring the same ERG11 mutations and exhibiting a fluconazole MIC as low as 1 mg/liter have been described previously”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [8] Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, Tarai B, Singh A, Upadhyaya G, Upadhyay S, Yadav P, Singh PK, Khillan V, Sachdeva N, Perlin DS, Meis JF 2018 A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother 73: 891– 899. doi: 10.1093/jac/dkx480. 29325167 source
Not checked in the free run.
- cites [14] Escandon P, Chow NA, Caceres DH, Gade L, Berkow EL, Armstrong P, Rivera S, Misas E, Duarte C, Moulton-Meissner H, Welsh RM, Parra C, Pescador LA, Villalobos N, Salcedo S, Berrio I, Varon C, Espinosa-Bode A, Lockhart SR, Jackson BR, Litvintseva AP, Beltran M, Chiller TM 2019 Molecular epidemiology of Candida auris in Colombia reveals a highly related, countrywide colonization with regional patterns in amphotericin B resistance. Clin Infect Dis 68: 15– 21. doi: 10.1093/cid/ciy411. 29788045 source
Not checked in the free run.
- Interpretationown data
Mutations in TAC1B significantly contribute to clinical fluconazole resistance in Candida auris.
“In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance.”
- Also stated in: § INTRODUCTION · boosted
“demonstrating that mutations in TAC1B represent prevalent and significant genetic determinants of fluconazole resistance among clinical C. auris isolates.”
Quote in the paperSubstantial claim - Also stated in: § INTRODUCTION · boosted
- Premisecitation
Heterologous expression of Candida auris ERG11 alleles carrying Y132F or K143R on a low-copy-number episomal plasmid decreased fluconazole susceptibility in a haploid Saccharomyces cerevisiae strain.
“heterologous expression of C. auris ERG11 alleles carrying mutations encoding either the Y132F or K143R amino acid substitution on a low-copy-number episomal plasmid was observed to decrease fluconazole susceptibility in a haploid strain of Saccharomyces cerevisiae (13).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [13] Healey KR, Kordalewska M, Jimenez Ortigosa C, Singh A, Berrio I, Chowdhary A, Perlin DS 24 9 2018, posting date Limited ERG11 mutations identified in isolates of Candida auris directly contribute to reduced azole susceptibility. Antimicrob Agents Chemother doi: 10.1128/AAC.01427-18. PMC6153782 30082281 source
Not checked in the free run.
- Interpretationown data
Mutations in TAC1B represent a potent genetic determinant contributing to clinical fluconazole resistance in C. auris.
“the findings of these studies serve to demonstrate that mutations in TAC1B both represent a potent genetic determinant contributing to clinical fluconazole resistance in C. auris”
Quote in the paperSubstantial claim - Study design and conductown data
The glucose starvation conditions used in this study were adequate to remove CDR1 activity.
“confirming that the conditions used in this study for glucose starvation were adequate to remove the activity of this known C. auris resistance effector.”
Quote in the paperSubstantial claim - Premisecitation
The level of CDR1 expression in the evolved strains is similar to that previously described among extensively fluconazole-resistant Candida auris clinical isolates.
“This level of CDR1 expression is similar to that previously described among extensively fluconazole-resistant C. auris clinical isolates (20).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Rybak JM, Doorley LA, Nishimoto AT, Barker KS, Palmer GE, Rogers PD 27 3 2019, posting date Abrogation of triazole resistance upon deletion of CDR1 in a clinical isolate of Candida auris. Antimicrob Agents Chemother doi: 10.1128/AAC.00057-19. PMC6437491 30718246 source
Not checked in the free run.
- Interpretationown data
Mutations in C. auris TAC1B represent a novel genetic determinant of clinical fluconazole resistance.
“these data definitively demonstrate that mutations in C. auris TAC1B represent a novel genetic determinant of clinical fluconazole resistance”
Quote in the paperSubstantial claim - Interpretationreasoning
The changes in sterol profile of AR0387 may be related to the lower fluconazole MIC for this clinical isolate (1 mg/liter).
“these changes in the sterol profile of AR0387 may be related to the lower fluconazole MIC for this clinical isolate (1 mg/liter)”
Quote in the paperNot a substantial claim - Interpretationown data
TAC1B mutations may provide additive fluconazole resistance effects with ERG11 mutations.
“suggesting that these mutations may provide additive fluconazole resistance effects.”
Quote in the paperSubstantial claim - Premisecitation
A notable proportion of C. auris clinical isolates have increased copy numbers of resistance-associated genes.
“a notable proportion of C. auris clinical isolates have been observed to exhibit increased copy numbers of resistance-associated genes”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] Chow NA, Muñoz JF, Gade L, Berkow E, Li X, Welsh RM, Forsberg K, Lockhart SR, Adam R, Alanio A, Alastruey-Izquierdo A, Althawadi S, Belén Araúz A, Ben-Ami R, Bharat A, Calvo B, Desnos-Ollivier M, Escandón P, Gardam D, Gunturu R, Heath CH, Kurzai O, Martin R, Litvintseva AP, Cuomo CA 2020 Tracing the evolutionary history and global expansion of Candida auris using population genomic analyses. bioRxiv doi: 10.1101/2020.01.06.896548. PMC7188998 32345637 source
Not checked in the free run.
- Interpretationown data
Mutations in TAC1B are prevalent among the members of a large global collection of fluconazole-resistant clinical isolates.
“and are prevalent among the members of a large global collection of fluconazole-resistant clinical isolates”
Quote in the paperSubstantial claim - Interpretationown data
Candida auris A657V corresponds to the CaTac1 gain-of-function mutation A736V associated with increased triazole resistance in Candida albicans.
“C. auris A657V corresponds to the CaTac1 GOF mutation A736V associated with increased triazole resistance in C. albicans.”
Quote in the paperSubstantial claim - Interpretationcitation
The change in sterol profile of AR0387 under fluconazole treatment is consistent with previously reported changes in fungal sterols with suprainhibitory concentrations of fluconazole.
“this change in the sterol profile of AR0387 under conditions of fluconazole treatment is consistent with previously reported changes in fungal sterols with suprainhibitory concentrations of fluconazole (33, 35)”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [33] Martel CM, Parker JE, Bader O, Weig M, Gross U, Warrilow AG, Kelly DE, Kelly SL 2010 A clinical isolate of Candida albicans with mutations in ERG11 (encoding sterol 14alpha-demethylase) and ERG5 (encoding C22 desaturase) is cross resistant to azoles and amphotericin B. Antimicrob Agents Chemother 54: 3578– 3583. doi: 10.1128/AAC.00303-10. 20547793 PMC2934972 source
Not checked in the free run.
- cites [35] Parker JE, Merkamm M, Manning NJ, Pompon D, Kelly SL, Kelly DE 2008 Differential azole antifungal efficacies contrasted using a Saccharomyces cerevisiae strain humanized for sterol 14 alpha-demethylase at the homologous locus. Antimicrob Agents Chemother 52: 3597– 3603. doi: 10.1128/AAC.00517-08. 18694951 PMC2565906 source
Not checked in the free run.
- Interpretationown data
Similarities between the fluconazole-evolved strains and clinical isolates of Candida possessing known GOF mutations in close homologs of TAC1B are apparent, such as increased expression of CDR1.
“while similarities between the fluconazole-evolved strains in this work and clinical isolates of Candida possessing known GOF mutations in close homologs of TAC1B are apparent, such as the increased expression of CDR1”
Quote in the paperNot a substantial claim
- The quote only partly states this claim. 1
- May combine two claims. 14
- Classified as probably not a substantial claim. 19
The quote only partly states this claim.
Findingown dataIn all samples grown without fluconazole, ergosterol comprised more than 75% of total cellular sterols.
“In all samples, ergosterol comprised more than 75% of total cellular sterols”
Quote in the paperNot a substantial claimMay combine two claims.
Findingnone givenNeither R495G nor F214S corresponds to previously characterized gain-of-function mutations in CaTAC1 or orthologous genes from other Candida species.
“Neither of these mutations corresponds to previously characterized GOF mutations in CaTAC1 or to orthologous genes from other species of Candida.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataA640V was the most common TAC1B mutation among clinical isolates, found in 57 clade I isolates from 7 countries and always present with the ERG11 K143R mutation.
“a mutation encoding the A640V amino acid substitution was found to be the most common among clinical isolates, found in 57 clade I isolates from 7 countries and always present with the ERG11 mutation encoding the K143R amino acid substitution.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTwo different mutations affecting the P595 site were observed: P595L in clade I and P595H in clade IV.
“two different mutations affecting the P595 site (P595L in clade I and P595H in clade IV).”
Quote in the paperNot a substantial claimMay combine two claims.
FindingcitationThe second-generation fluconazole-evolved FLU-A2 strain had increased TAC1B copy numbers and harbored a R495G-encoding mutation in TAC1B.
“the increased TAC1B copy numbers seen in the second-generation fluconazole-evolved FLU-A2 strain (which concomitantly harbored a R495G-encoding mutation in TAC1B)”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataFLU-A2 showed a 2-fold increase in TAC1B copy number, which was not evident in other evolved strains.
“the second-generation fluconazole-evolved FLU-A2 strain was found to show a 2-fold increase in the copy number of TAC1B, which was not evident in other evolved strains”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data14-methyl-ergosta-8,24(28)-dienol-3,6-diol comprised 3.8% ± 1.9% of all sterols in AR0387 grown with fluconazole, while it was absent in all fluconazole-evolved strains.
“14-methyl-ergosta-8,24(28)-dienol-3,6-diol comprised 3.8% ± 1.9% all sterols present in AR0387, while this sterol was absent in the sterol profiles of all fluconazole-evolved strains.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataA657V and F862_N866del appeared in isolates with the ERG11 Y132F variant, and these isolates had markedly high MIC values.
“These mutations appeared in isolates with the ERG11 Y132F variant, and these isolates were found to have markedly high MIC values”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataOther common TAC1B mutations included A657V in 15 clade I isolates and the frameshift mutation F862_N866del in 46 clade IV isolates.
“Other common TAC1B mutations found included A657V in 15 clade I isolates and the frameshift mutation F862_N866del in 46 clade IV isolates.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationIncreased expression of efflux pump-encoding genes is a common contributor to clinical triazole resistance among multiple Candida species.
“increased expression of efflux pump-encoding genes is a common contributor to clinical triazole resistance among multiple species of Candida (15).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Whaley SG, Berkow EL, Rybak JM, Nishimoto AT, Barker KS, Rogers PD 2016 Azole antifungal resistance in Candida albicans and emerging non-albicans Candida species. Front Microbiol 7: 2173. doi: 10.3389/fmicb.2016.02173. 28127295 PMC5226953 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn Candida glabrata, nearly all clinical triazole resistance is attributable to overexpression of CgCDR1, CgPDH1, and CgSNQ2.
“in which nearly all of the clinical triazole resistance is attributable to overexpression of the ATP-binding cassette (ABC)-type efflux pump-encoding genes C. glabrata CDR1 (CgCDR1), CgPDH1, and CgSNQ2 (16).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Whaley SG, Zhang Q, Caudle KE, Rogers PD 24 11 2018, posting date Relative contribution of the ABC transporters Cdr1, Pdh1, and Snq2 to azole resistance in Candida glabrata. Antimicrob Agents Chemother doi: 10.1128/AAC.01070-18. PMC6153852 30038038 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe Candida auris genome includes a substantial number of efflux pump-encoding genes of both ABC and major facilitator superfamily classes.
“The C. auris genome has recently been revealed to include a substantial number of efflux pump-encoding genes of both the ABC and major facilitator superfamily (MFS) classes”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [17] Ben-Ami R, Berman J, Novikov A, Bash E, Shachor-Meyouhas Y, Zakin S, Maor Y, Tarabia J, Schechner V, Adler A, Finn T 13 1 2017, posting date Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel. Emerg Infect Dis doi: 10.3201/eid2302.161486. PMC5324804 28098529 source
Not checked in the free run.
- cites [18] Munoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, Farrer RA, Litvintseva AP, Cuomo CA 2018 Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun 9: 5346. doi: 10.1038/s41467-018-07779-6. 30559369 PMC6297351 source
Not checked in the free run.
- cites [19] Wasi M, Khandelwal NK, Moorhouse AJ, Nair R, Vishwakarma P, Bravo Ruiz G, Ross ZK, Lorenz A, Rudramurthy SM, Chakrabarti A, Lynn AM, Mondal AK, Gow NAR, Prasad R 2019 ABC transporter genes show upregulated expression in drug-resistant clinical isolates of Candida auris: a genome-wide characterization of ATP-binding cassette (ABC) transporter genes. Front Microbiol 10: 1445. doi: 10.3389/fmicb.2019.01445. 31379756 PMC6647914 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationApproximately 90% of Candida auris clinical isolates are resistant to fluconazole (MIC, ≥32 mg/liter; modal MIC, ≥256 mg/liter).
“90% are resistant to fluconazole (MIC, ≥32mg/liter; modal MIC, ≥256mg/liter) (6).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [6] Anonymous. 2020 Candida auris: antifungal susceptibility testing and interpretation. Centers for Disease Control and Prevention, Atlanta, GA https://www.cdc.gov/fungal/candida-auris/c-auris-antifungal.html. Accessed January 16th.
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationIncreased expression of the Candida auris ABC-type efflux pump-encoding gene CDR1 has previously been shown to substantially contribute to clinical triazole resistance.
“the increased expression of the C. auris ABC-type efflux pump-encoding gene CDR1 has previously been shown to substantially contribute to clinical triazole resistance (20, 21).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [20] Rybak JM, Doorley LA, Nishimoto AT, Barker KS, Palmer GE, Rogers PD 27 3 2019, posting date Abrogation of triazole resistance upon deletion of CDR1 in a clinical isolate of Candida auris. Antimicrob Agents Chemother doi: 10.1128/AAC.00057-19. PMC6437491 30718246 source
Not checked in the free run.
- cites [21] Kim SH, Iyer KR, Pardeshi L, Munoz JF, Robbins N, Cuomo CA, Wong KH, Cowen LE 2019 Genetic analysis of Candida auris implicates Hsp90 in morphogenesis and azole tolerance and Cdr1 in azole resistance. mBio 10: e00346-19. doi: 10.1128/mBio.00346-19. 30696744 PMC6355988 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationCandida auris is an emerging multidrug-resistant pathogen of global concern, responsible for outbreaks on six continents and commonly resistant to antifungals.
“Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [1] Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H 2009 Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol 53: 41– 44. doi: 10.1111/j.1348-0421.2008.00083.x. 19161556 source
Not checked in the free run.
- cites [2] Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP 2017 Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis 64: 134– 140. doi: 10.1093/cid/ciw691. 27988485 PMC5215215 source
Not checked in the free run.
May combine two claims.
PremisecitationERG11 mutations encoding VF125AL (F126L), Y132F, and K143R are frequently reported among fluconazole-resistant Candida auris clinical isolates and are associated with specific genetic clades.
“Three such mutations, encoding the amino acid substitutions VF125AL (commonly referred to as F126L), Y132F, and K143R, are frequently reported among fluconazole-resistant clinical isolates, and associations between these mutations and specific genetic clades of C. auris have been observed (2).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [2] Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP 2017 Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis 64: 134– 140. doi: 10.1093/cid/ciw691. 27988485 PMC5215215 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll susceptibility testing was performed in technical triplicate and biological duplicate.
“All susceptibility testing was performed in technical triplicate and biological duplicate.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationClinical isolates of Candida with reduced fluconazole sensitivity may exhibit altered fluconazole uptake.
“it is has been suggested that clinical isolates of Candida with reduced fluconazole sensitivity may exhibit altered fluconazole uptake (24)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] Mansfield BE, Oltean HN, Oliver BG, Hoot SJ, Leyde SE, Hedstrom L, White TC 2010 Azole drugs are imported by facilitated diffusion in Candida albicans and other pathogenic fungi. PLoS Pathog 6: e1001126. doi: 10.1371/journal.ppat.1001126. 20941354 PMC2947996 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataFluconazole MICs did not differ between independent transformants.
“The fluconazole MICs did not differ between independent transformants.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown data[3H]fluconazole uptake experiments were performed with six biological replicates.
“Experiments were performed with six biological replicates”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMultiple mutations encoding amino acid substitutions in the middle homology region of CaTAC1 have previously been reported to be associated with fluconazole resistance.
“multiple mutations encoding amino acid substitutions in the MHR of CaTAC1 have previously been reported to be associated with fluconazole resistance (25).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] Nishimoto AT, Sharma C, Rogers PD 1 2 2019, posting date Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus Candida albicans. J Antimicrob Chemother doi: 10.1093/jac/dkz400. PMC8204710 31603213 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataFluconazole susceptibility testing was included for 294 of the 304 isolates included in whole-genome analyses.
“Fluconazole susceptibility testing was included for 294 of the 304 isolates included in whole-genome analyses.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll qPCR and RT-qPCR experiments were performed in biological and technical triplicate.
“All experiments were performed in biological and technical triplicate.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll sterol analysis was performed in biological triplicate.
“All sterol analysis was performed in biological triplicate.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataR495G and F214S are predicted to alter residues near or within the conserved fungal transcription factor middle homology region of Tac1Bp.
“these mutations are predicted to alter residues near or within the conserved fungal transcription factor middle homology region (MHR) of Tac1Bp”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe in vitro evolution experiments were performed in a single genetic background and using only fluconazole.
“The in vitro evolution experiments described were performed in a single genetic background and using only fluconazole.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataAll final strains that lost the SAT1-FLP cassette were confirmed by sequencing.
“All final strains that were identified as having lost the SAT1-FLP cassette by replica plating as previously described were then again confirmed by sequencing”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Interpretationown dataThe maintained ergosterol content observed in fluconazole-evolved strains may be a direct consequence of the identified mutations in C. auris TAC1B or a result of the decreased fluconazole sensitivity of these fluconazole-evolved strains.
“the maintained ergosterol content observed in fluconazole-evolved strains may be a direct consequence of the identified mutations in C. auris TAC1B or a result of the decreased fluconazole sensitivity of these fluconazole-evolved strains”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown dataIntegration of the repair template at the targeted loci was confirmed by PCR for all transformants.
“Integration of the repair template at the targeted loci was then confirmed by PCR for all transformants.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningIt cannot be determined if different mechanisms of triazole resistance would be observed if similar studies were conducted with different clinical isolates of C. auris or different agents of the triazole class of antifungals.
“it cannot be determined if different mechanisms of triazole resistance would be observed if similar studies were conducted with different clinical isolates of C. auris or different agents of the triazole class of antifungals”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataMutations in TAC1B represent prevalent and significant genetic determinants of fluconazole resistance among clinical Candida auris isolates.
“demonstrating that mutations in TAC1B represent prevalent and significant genetic determinants of fluconazole resistance among clinical C. auris isolates.”
Quote in the paperSubstantial claim
The paper relies on this without support.
Little is known about the molecular mechanisms of fluconazole resistance in Candida auris.
“relatively little is known about the molecular mechanisms underpinning this resistance.”
The paper relies on this without support.
The genetic determinants underpinning increased expression of efflux pump-encoding genes in Candida auris remain unidentified.
“At present, however, the genetic determinants underpinning the increased expression of efflux pump-encoding genes in C. auris remain unidentified.”
The paper relies on this without support.
The presence of ERG11 mutations alone poorly explains the entirety of clinical fluconazole resistance in Candida auris.
“the presence of this mechanism alone poorly explains the entirety of resistance observed clinically”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Gain-of-function mutations in TAC1B and MRR1A contribute to clinical fluconazole resistance in C. auris.
“Likewise, gain-of-function mutations in TAC1B (C. auris homologue of C. albicans TAC1) and MRR1A (C. auris homologue of C. albicans MRR1) contribute to clinical fluconazole resistance in C. auris54,55.”
From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [54]
A study of 304 globally distributed C. auris clinical isolates representing four major genetic clades identified three predominant TAC1B mutations encoding A640V, A657V, and F862_N866del substitutions from clades Ic, Ib, and IV, respectively.
“For example, a study examining 304 globally-distributed C. auris clinical isolates representing each of four of the major genetic clades identified three predominant TAC1B mutations, encoding A640V, A657V, and F862_N866del substitutions, from clades Ic, Ib, and IV, respectively54.”
From Molecular mechanisms governing antifungal drug resistance (2023) · cites this paper as [54]
AR0390 carries a mutation encoding the A640V substitution in the transcription factor Tac1B which likely leads to overexpression of the Cdr1 drug efflux transporter.
“AR0390 also carries a mutation (encoding the A640V substitution) in the gene encoding the transcription factor Tac1B which likely leads to overexpression of the Cdr1 drug efflux transporter (15, 16).”
From Delineation of the Direct Contribution of Candida auris <i>ERG11</i> Mutations to Clinical Triazole Resistance (2021) · cites this paper as [15]
Correction of the TAC1B A640V mutation to wild type in AR0390 confers susceptibility to fluconazole with an MIC of 16 mg/L.
“Correction of this mutation to the wild type sequence in clinical isolate AR0390 likewise confers susceptibility to fluconazole with an MIC of 16 mg/L.”
From Delineation of the Direct Contribution of Candida auris <i>ERG11</i> Mutations to Clinical Triazole Resistance (2021) · cites this paper as [15]
Transformants were confirmed by Sanger sequencing to possess each of the four ERG11 alleles of interest.
“transformations were performed by electroporation to generate transformants which were confirmed by Sanger sequencing to possess each of the four ERG11 alleles of interest as previously described (15, 16).”
From Delineation of the Direct Contribution of Candida auris <i>ERG11</i> Mutations to Clinical Triazole Resistance (2021) · cites this paper as [15]
Transformants were confirmed to possess a single copy of ERG11 by qPCR.
“Additionally, transformants were confirmed to possess a single copy of ERG11 by qPCR as previously described (15).”
From Delineation of the Direct Contribution of Candida auris <i>ERG11</i> Mutations to Clinical Triazole Resistance (2021) · cites this paper as [15]
MIC determination was performed by broth microdilution in biological duplicate, each with three technical replicates, and MIC from biological replicates were in agreement.
“A modified CLSI MIC determination employing the standard endpoint of 50% growth inhibition was performed using broth microdilution in biological duplicate, each with three technical replicates, as previously described, and MIC from biological replicates were in agreement (15).”
From Delineation of the Direct Contribution of Candida auris <i>ERG11</i> Mutations to Clinical Triazole Resistance (2021) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Fluconazole concentration differs 1,000-fold between methods and results
MajorThe gene-expression methods specify 16 mg/ml of fluconazole, whereas the experimental concentration described elsewhere is 16 mg/liter. These differ by a factor of 1,000.
Reported 16 · recomputed 16000
“10 ml of RPMI media with or without 16 mg/ml of fluconazole”
Glucose-starvation duration differs between results and methods
MinorThe results describe measuring fluconazole accumulation after 2 hours of glucose starvation, but the uptake methods specify 3 hours.
“following 2 h glucose starvation in YNB media without carbon source supplementation”
“C. auris isolates and fluconazole-evolved strains were subjected to glucose starvation for 3 h”
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607 · see citing works
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data
McKenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A., Garimella, K., Altshuler, D., Gabriel, S., Daly, M., et al. (2010) · Genome Research · doi:10.1101/gr.107524.110 · Cited by 27,895 · see citing works
Cingolani, P., Platts, A., Wang, L. L., Coon, M., Nguyen, T., Wang, L., Land, S. J., Lu, X., & Ruden, D. M. (2012) · Fly · doi:10.4161/fly.19695 · Cited by 11,816 · see citing works
Quality control and preprocessing of metagenomic datasets
Schmieder, R., & Edwards, R. A. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr026 · Cited by 4,989 · see citing works
Lockhart, S. R., Etienne, K. A., Vallabhaneni, S., Farooqi, J., Chowdhary, A., Govender, N. P., Colombo, A. L., Calvo, B., Cuomo, C. A., Desjardins, C. A., et al. (2017) · Clinical Infectious Diseases · doi:10.1093/cid/ciw691 · Cited by 1,662 · see citing works
Self-citationSatoh, K., Makimura, K., Hasumi, Y., Nishiyama, Y., Uchida, K., & Yamaguchi, H. (2009) · Microbiology and Immunology · doi:10.1111/j.1348-0421.2008.00083.x · Cited by 1,381 · see citing works
Azole Antifungal Resistance in Candida albicans and Emerging Non-albicans Candida Species
Whaley, S. G., Berkow, E. L., Rybak, J. M., Nishimoto, A. T., Barker, K. S., & Rogers, P. D. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.02173 · Cited by 900 · see citing works
Self-citationChowdhary, A., Prakash, A., Sharma, C., Kordalewska, M., Kumar, A., Sarma, S., Tarai, B., Singh, A., Upadhyaya, G., Upadhyay, S., et al. (2018) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkx480 · Cited by 577 · see citing works
Chow, N. A., Muñoz, J. F., Gade, L., Berkow, E., Li, X., Welsh, R. M., Forsberg, K., Lockhart, S. R., Adam, R., Alanio, A., et al. (2020) · doi:10.1101/2020.01.06.896548 · Cited by 463 · see citing works
Self-citationMuñoz, J. F., Gade, L., Chow, N. A., Loparev, V. N., Juieng, P., Berkow, E. L., Farrer, R. A., Litvintseva, A. P., & Cuomo, C. A. (2018) · Nature Communications · doi:10.1038/s41467-018-07779-6 · Cited by 458 · see citing works
Self-citationCoste, A. T., Karababa, M., Ischer, F., Bille, J., & Sanglard, D. (2004) · Eukaryotic Cell · doi:10.1128/ec.3.6.1639-1652.2004 · Cited by 407 · see citing works
Kelly, S. L., Lamb, D. C., Kelly, D. E., Manning, N. J., Loeffler, J., Hebart, H., Schumacher, U., & Einsele, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(96)01360-9 · Cited by 351 · see citing works
Self-citationThe evolution of drug resistance in clinical isolates of Candida albicans.
Ford, C. B., Funt, J. M., Abbey, D., Issi, L., Guiducci, C., Martinez, D. A., Delorey, T., Li, B. Y., White, T. C., Cuomo, C., et al. (2015) · eLife · doi:10.7554/elife.00662 · Cited by 348 · see citing works
Self-citationMultidrug-Resistant <i>Candida haemulonii</i> and <i>C. auris</i> , Tel Aviv, Israel
Ben-Ami, R., Berman, J., Novikov, A., Bash, E., Shachor-Meyouhas, Y., Zakin, S., Maor, Y., Tarabia, J., Schechner, V., Adler, A., et al. (2017) · Emerging Infectious Diseases · doi:10.3201/eid2302.161486 · Cited by 297 · see citing works
Contribution of Clinically Derived Mutations in <i>ERG11</i> to Azole Resistance in Candida albicans
Flowers, S. A., Colón, B., Whaley, S. G., Schuler, M. A., & Rogers, P. D. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03470-14 · Cited by 294 · see citing works
Self-citationDunkel, N., Blaß, J., Rogers, P. D., & Morschhäuser, J. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06309.x · Cited by 278 · see citing works
Self-citationCandida auris Isolates Resistant to Three Classes of Antifungal Medications — New York, 2019
Ostrowsky, B. E., Greenko, J. A., Adams, E. H., Quinn, M., O’Brien, B., Chaturvedi, V. P., Berkow, E. L., Vallabhaneni, S., Forsberg, K., Chaturvedi, S., et al. (2020) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6901a2 · Cited by 247 · see citing works
Self-citationFlowers, S. A., Barker, K. S., Berkow, E. L., Toner, G., Chadwick, S. G., Gygax, S. E., Morschhäuser, J., & Rogers, P. D. (2012) · Eukaryotic Cell · doi:10.1128/ec.00215-12 · Cited by 239 · cited 13× · see citing works
“In this organism, the most commonly reported mechanisms of fluconazole resistance include mutations in the gene encoding the target of the triazole antifungals, CaERG11 , and overexpression of either CaERG11 or genes encoding multidrug-efflux pumps such as CaCDR1 , CaCDR2 , and CaMDR1 (12, 15, 28).”
InfluentialSelf-citationDunkel, N., Liu, T. T., Barker, K. S., Homayouni, R., Morschhäuser, J., & Rogers, P. D. (2008) · Eukaryotic Cell · doi:10.1128/ec.00103-08 · Cited by 236 · see citing works
Self-citationEscandón, P., Chow, N. A., Caceres, D. H., Gade, L., Berkow, E. L., Armstrong, P., Rivera, S., Misas, E., Duarte, C., Moulton-Meissner, H., et al. (2019) · Clinical Infectious Diseases · doi:10.1093/cid/ciy411 · Cited by 222 · see citing works
Self-citationCandida auris and multidrug resistance: Defining the new normal
Lockhart, S. R. (2019) · Fungal Genetics and Biology · doi:10.1016/j.fgb.2019.103243 · Cited by 205 · see citing works
Self-citationMartel, C. M., Parker, J. E., Bader, O., Weig, M., Gross, U., Warrilow, A. G. S., Rolley, N., Kelly, D. E., & Kelly, S. L. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00348-10 · Cited by 168 · see citing works
Self-citationMartel, C. M., Parker, J. E., Bader, O., Weig, M., Gross, U., Warrilow, A. G. S., Kelly, D. E., & Kelly, S. L. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00303-10 · Cited by 165 · see citing works
Self-citationHealey, K. R., Kordalewska, M., Jiménez Ortigosa, C., Singh, A., Berrío, I., Chowdhary, A., & Perlin, D. S. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01427-18 · Cited by 165 · see citing works
Rybak, J. M., Doorley, L. A., Nishimoto, A. T., Barker, K. S., Palmer, G. E., & Rogers, P. D. (2019) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00057-19 · Cited by 141 · see citing works
Self-citationKim, S. H., Iyer, K. R., Pardeshi, L., Muñoz, J. F., Robbins, N., Cuomo, C. A., Wong, K. H., & Cowen, L. E. (2019) · mBio · doi:10.1128/mbio.02529-18 · Cited by 136 · see citing works
Self-citationAzole Drugs Are Imported By Facilitated Diffusion in Candida albicans and Other Pathogenic Fungi
Mansfield, B. E., Oltean, H. N., Oliver, B. G., Hoot, S. J., Leyde, S. E., Hedstrom, L., & White, T. C. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1001126 · Cited by 111 · see citing works
Self-citationCandida auris: A Review of Recommendations for Detection and Control in Healthcare Settings
Caceres, D. H., Forsberg, K., Welsh, R. M., Sexton, D. J., Lockhart, S. R., Jackson, B. R., & Chiller, T. M. (2019) · Journal of Fungi · doi:10.3390/jof5040111 · Cited by 110 · see citing works
Self-citationBhattacharya, S., Holowka, T., Orner, E. P., & Fries, B. C. (2019) · Scientific Reports · doi:10.1038/s41598-019-41513-6 · Cited by 104 · see citing works
Nishimoto, A. T., Sharma, C., & Rogers, P. D. (2020) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkz400 · Cited by 102 · see citing works
Self-citationWasi, M., Khandelwal, N. K., Moorhouse, A. J., Nair, R., Vishwakarma, P., Bravo Ruiz, G., Ross, Z. K., Lorenz, A., Rudramurthy, S. M., Chakrabarti, A., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.01445 · Cited by 89 · see citing works
Analysis of Candida auris fungemia at a single facility in Kenya
Adam, R. D., Revathi, G., Okinda, N., Fontaine, M., Shah, J., Kagotho, E., Castanheira, M., Pfaller, M. A., & Maina, D. (2019) · International Journal of Infectious Diseases · doi:10.1016/j.ijid.2019.06.001 · Cited by 70 · see citing works
Whaley, S. G., Zhang, Q., Caudle, K. E., & Rogers, P. D. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01070-18 · Cited by 59 · see citing works
Self-citationOngoing Challenges with Healthcare-Associated Candida auris Outbreaks in Oman
Al-Maani, A. S., Paul, H. E., Al-Rashdi, A., Wahaibi, A. S. A., Al‐Jardani, A., AlAbri, A., Al-Balushi, M. K., Al-Abri, S., Reesi, M. A., Maqbali, A. A., et al. (2019) · Journal of Fungi · doi:10.3390/jof5040101 · Cited by 57 · see citing works
Rybak, J. M., Dickens, C. M., Parker, J. E., Caudle, K. E., Manigaba, K., Whaley, S. G., Nishimoto, A. T., Luna-Tapia, A., Roy, S., Zhang, Q., et al. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00651-17 · Cited by 53 · see citing works
Self-citationLiu, Z., & Myers, L. C. (2017) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01342-17 · Cited by 52 · see citing works
Fluconazole penetration in cerebral parenchyma in humans at steady state
Thaler, F., Bernard, B., Tod, M. M., Jedynak, C. P., Petitjean, O., Derome, P., & Loirat, P. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.5.1154 · Cited by 50 · see citing works
Parker, J. E., Merkamm, M., Manning, N. J., Pompon, D., Kelly, S. L., & Kelly, D. E. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00517-08 · Cited by 46 · see citing works
Self-citationTrends in antifungal use in US hospitals, 2006–12
Vallabhaneni, S., Baggs, J., Tsay, S., Srinivasan, A. R., Jernigan, J. A., & Jackson, B. R. (2018) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dky270 · Cited by 45 · see citing works
Kim, S. H., Iyer, K. R., Pardeshi, L., Muñoz, J. F., Robbins, N., Cuomo, C. A., Wong, K. H., & Cowen, L. E. (2019) · mBio · doi:10.1128/mbio.00346-19 · Cited by 28 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- CLSI. 2017. Reference method for broth dilution antifungal susceptibility testing of yeast; approved standard-4th ed. Clinical and Laboratory Standards Institute, Wayne, PA.
Cited by
Sorted by citations
Antifungal Drug Resistance: Molecular Mechanisms in <i>Candida albicans</i> and Beyond
Lee, Y., Puumala, E., Robbins, N., & Cowen, L. E. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00199 · Cited by 801 · see citing works
Candida auris: Epidemiology, biology, antifungal resistance, and virulence
Du, H., Bing, J., Hu, T., Ennis, C. L., Nobile, C. J., & Huang, G. (2020) · PLOS Pathogens · doi:10.1371/journal.ppat.1008921 · Cited by 609 · see citing works
The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin
Hoenigl, M., Sprute, R., Egger, M., Arastehfar, A., Cornely, O. A., Krause, R., Lass-Flörl, C., Prattes, J., Spec, A., Thompson, G. R., et al. (2021) · Drugs · doi:10.1007/s40265-021-01611-0 · Cited by 467 · see citing works
Chow, N. A., Muñoz, J. F., Gade, L., Berkow, E., Li, X., Welsh, R. M., Forsberg, K., Lockhart, S. R., Adam, R., Alanio, A., et al. (2020) · doi:10.1101/2020.01.06.896548 · Cited by 463 · see citing works
Self-citationMolecular mechanisms governing antifungal drug resistance
Lee, Y., Robbins, N., & Cowen, L. E. (2023) · npj Antimicrobials and Resistance · doi:10.1038/s44259-023-00007-2 · Cited by 304 · see citing works
Ahmad, S., & Alfouzan, W. (2021) · Microorganisms · doi:10.3390/microorganisms9040807 · Cited by 269 · see citing works
Carolus, H., Pierson, S., Muñoz, J. F., Subotić, A., Cruz, R. B., Cuomo, C. A., & Van Dijck, P. (2021) · mBio · doi:10.1128/mbio.03333-20 · Cited by 211 · see citing works
Self-citationConfirmation of fifth <i>Candida auris</i> clade by whole genome sequencing
Spruijtenburg, B., Badali, H., Abastabar, M., Mirhendi, H., Khodavaisy, S., Sharifisooraki, J., Taghizadeh Armaki, M., de Groot, T., & Meis, J. F. (2022) · Emerging Microbes & Infections · doi:10.1080/22221751.2022.2125349 · Cited by 164 · see citing works
<i>Candida auris</i> Genetics and Emergence
Chowdhary, A., Jain, K., & Chauhan, N. (2023) · Annual Review of Microbiology · doi:10.1146/annurev-micro-032521-015858 · Cited by 158 · see citing works
The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens
Arastehfar, A., Lass-Flörl, C., Garcia-Rubio, R., Daneshnia, F., Ilkit, M., Boekhout, T., Gabaldon, T., & Perlin, D. S. (2020) · Journal of Fungi · doi:10.3390/jof6030138 · Cited by 145 · see citing works
Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in <i>Candida auris</i>
Muñoz, J. F., Welsh, R. M., Shea, T., Batra, D., Gade, L., Howard, D., Rowe, L. A., Meis, J. F., Litvintseva, A. P., & Cuomo, C. A. (2021) · Genetics · doi:10.1093/genetics/iyab029 · Cited by 125 · see citing works
Self-citationRybak, J. M., Barker, K. S., Muñoz, J. F., Parker, J. E., Ahmad, S., Mokaddas, E., Abdullah, A., Elhagracy, R. S., Kelly, S. L., Cuomo, C. A., et al. (2022) · Clinical Microbiology and Infection · doi:10.1016/j.cmi.2021.11.024 · Cited by 120 · see citing works
Self-citationRybak, J. M., Cuomo, C. A., & David Rogers, P. (2022) · Current Opinion in Microbiology · doi:10.1016/j.mib.2022.102208 · Cited by 113 · see citing works
Self-citationSantana, D. J., & O’Meara, T. R. (2021) · Nature Communications · doi:10.1038/s41467-021-27545-5 · Cited by 91 · see citing works
Burrack, L. S., Todd, R. T., Soisangwan, N., Wiederhold, N. P., & Selmecki, A. (2022) · mBio · doi:10.1128/mbio.00842-22 · Cited by 82 · see citing works
Bing, J., Hu, T., Zheng, Q., Muñoz, J. F., Cuomo, C. A., & Huang, G. (2020) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01466-20 · Cited by 86 · see citing works
Self-citationNovel <i>ERG11</i> and <i>TAC1b</i> Mutations Associated with Azole Resistance in Candida auris
Li, J., Coste, A. T., Liechti, M., Bachmann, D., Sanglard, D., & Lamoth, F. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02663-20 · Cited by 82 · see citing works
Maphanga, T. G., Naicker, S. D., Kwenda, S., Muñoz, J. F., van Schalkwyk, E., Wadula, J., Nana, T., Ismail, A., Coetzee, J., Govind, C., et al. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00517-21 · Cited by 78 · see citing works
Self-citationRybak, J. M., Sharma, C., Doorley, L. A., Barker, K. S., Palmer, G. E., & Rogers, P. D. (2021) · Microbiology Spectrum · doi:10.1128/spectrum.01585-21 · Cited by 69 · see citing works
Self-citationDeciphering the Mrr1/Mdr1 Pathway in Azole Resistance of Candida auris
Li, J., Coste, A. T., Bachmann, D., Sanglard, D., & Lamoth, F. (2022) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00067-22 · Cited by 59 · see citing works
Antifungal Drug Concentration Impacts the Spectrum of Adaptive Mutations in <i>Candida albicans</i>
Todd, R. T., Soisangwan, N., Peters, S., Kemp, B., Crooks, T., Gerstein, A., & Selmecki, A. (2023) · Molecular Biology and Evolution · doi:10.1093/molbev/msad009 · Cited by 53 · see citing works
Asadzadeh, M., Mokaddas, E., Ahmad, S., Abdullah, A. A., de Groot, T., Meis, J. F., & Shetty, S. A. (2022) · Mycoses · doi:10.1111/myc.13419 · Cited by 55 · see citing works
Al-Obaid, I., Asadzadeh, M., Ahmad, S., Alobaid, K., Alfouzan, W., Bafna, R., Emara, M., & Joseph, L. (2022) · Journal of Fungi · doi:10.3390/jof8030267 · Cited by 39 · see citing works
Narayanan, A., Kumar, P., Chauhan, A., Kumar, M., Yadav, K., Banerjee, A., Sharma, R. D., Rudramurthy, S. M., Chakrabarti, A., Sanyal, K., et al. (2022) · mBio · doi:10.1128/mbio.03052-22 · Cited by 35 · see citing works
Upc2-mediated mechanisms of azole resistance in <i>Candida auris</i>
Li, J., Aubry, L., Brandalise, D., Coste, A. T., Sanglard, D., & Lamoth, F. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.03526-23 · Cited by 33 · see citing works
Transcriptome Signatures Predict Phenotypic Variations of Candida auris
Jenull, S., Tscherner, M., Kashko, N., Shivarathri, R., Stoiber, A., Chauhan, M., Petryshyn, A., Chauhan, N., & Kuchler, K. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.662563 · Cited by 32 · see citing works
Deng, Y., Xu, M., Li, S., Bing, J., Zheng, Q., Huang, G., Liao, W., Pan, W., & Tao, L. (2024) · PLOS Pathogens · doi:10.1371/journal.ppat.1012362 · Cited by 16 · see citing works
- Authors
- Rybak, J. M., Muñoz, J. F., Barker, K. S., Parker, J. E., Esquivel, B. D., Berkow, E. L., Lockhart, S. R., Gade, L., Palmer, G. E., White, T. C., Kelly, S. L., Cuomo, C. A., & Rogers, P. D.
- Affiliations
- University of Tennessee Health Science Center (US)
- Broad Institute (US)
- Swansea University (GB)
- University of Missouri–Kansas City (US)
- Centers for Disease Control and Prevention (US)
- Corresponding author
- Rogers, P. David
- ORCID
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2020-06-30
- Volume
- 11
- Issue
- 3
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC7218281
- OpenAlex
- W3025731814
- Semantic Scholar
- 5b37a4bcd85bce139722cd582bb154870dce56b9
- Cited by
- 202
- References
- 40
- Citations by year
- 2026: 33 · 2025: 43 · 2024: 31 · 2023: 31 · 2022: 24 · 2021: 29 · 2020: 11
- FWCI
- 3.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- HHS | NIH | National Institute of Allergy and Infectious Diseases (R01 A1058145, R01 AI131620)
- Broad Institute (U19AI110818)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Candida auris, fluconazole resistance, transcription factor mutations, antifungal resistance mechanisms, multidrug resistance, clinical isolates, fungal clades, emerging fungal pathogens
- MeSH terms
- Antifungal Agents, Candida, Fungal Proteins, Microbial Sensitivity Tests, Mutation, Transcription Factors, Fluconazole, Drug Resistance, Fungal
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
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