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Cited by 62Antifungal resistance and susceptibilityFungal and yeast genetics researchYeasts and Rust Fungi Studies

Comparative Genomics of Two Sequential Candida glabrata Clinical Isolates

Open access
Vale-Silva, Luis, Beaudoing, Emmanuel, Tran, Van Du T, Sanglard, Dominique·2017·G3 Genes|Genomes|Genetics
DOI 10.1534/g3.117.042887PMC PMC5555451

Published version of a preprint

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Abstract

Candida glabrata is an important fungal pathogen which develops rapid antifungal resistance in treated patients. It is known that azole treatments lead to antifungal resistance in this fungal species and that multidrug efflux transporters are involved in this process. Specific mutations in the transcriptional regulator PDR1 result in upregulation of the transporters. In addition, we showed that the PDR1 mutations can contribute to enhance virulence in animal models. In this study, we were interested to compare genomes of two specific C. glabrata-related isolates, one of which was azole susceptible (DSY562) while the other was azole resistant (DSY565). DSY565 contained a PDR1 mutation (L280F) and was isolated after a time-lapse of 50 d of azole therapy. We expected that genome comparisons between both isolates could reveal additional mutations reflecting host adaptation or even additional resistance mechanisms. The PacBio technology used here yielded 14 major contigs (sizes 0.18–1.6 Mb) and mitochondrial genomes from both DSY562 and DSY565 isolates that were highly similar to each other. Comparisons of the clinical genomes with the published CBS138 genome indicated important genome rearrangements, but not between the clinical strains. Among the unique features, several retrotransposons were identified in the genomes of the investigated clinical isolates. DSY562 and DSY565 each contained a large set of adhesin-like genes (101 and 107, respectively), which exceed by far the number of reported adhesins (63) in the CBS138 genome. Comparison between DSY562 and DSY565 yielded 17 nonsynonymous SNPs (among which the was the expected PDR1 mutation) as well as small size indels in coding regions (11) but mainly in adhesin-like genes. The genomes contained a DNA mismatch repair allele of MSH2 known to be involved in the so-called hyper-mutator phenotype of this yeast species and the number of accumulated mutations between both clinical isolates is consistent with the presence of a MSH2 defect. In conclusion, this study is the first to compare genomes of C. glabrata sequential clinical isolates using the PacBio technology as an approach. The genomes of these isolates taken in the same patient at two different time points exhibited limited variations, even if submitted to the host pressure.

AI snapshot

Written from the paper’s full text.

TL;DR

This study sequenced and compared two sequential *Candida glabrata* clinical isolates, azole-susceptible DSY562 and azole-resistant DSY565, using PacBio long-read assembly. The genomes were highly similar, with the expected PDR1 L280F resistance mutation, limited SNP/indel differences, extensive adhesin-like gene repertoires, and evidence consistent with an MSH2-associated hypermutator background.

Key findings

  • PacBio assembly yielded 14 major contigs for DSY562 and 15 for DSY565, with N50s of 1,178,607 bp and 1,064,616 bp, respectively; total assembled bases were 12,729,188 bp for DSY562 and 12,728,164 bp for DSY565, a difference of 1,024 nucleotides.
  • DSY562 and DSY565 differed by 17 nonsynonymous SNPs, including the expected PDR1 L280F substitution in DSY565, plus 11 indels in coding regions; most coding indels (7 of 11) were in adhesin-like genes.
  • DSY562 contained 101 adhesin-like genes and DSY565 contained 107, with 95 shared; this exceeds the 63 adhesins reported for CBS138. The two clinical genomes also contained retrotransposon-like Tkp5 genes, and DSY565 lacked Tkp5-7 while retaining a single LTR at that locus.
  • Compared with CBS138, the clinical isolates showed major chromosomal rearrangements, but DSY562 and DSY565 had highly similar chromosome arrangements; CHEF separations corresponded well to assembly predictions (R² = 0.981).

Methods

  • Two sequential *C. glabrata* isolates from an HIV-positive patient with oropharyngeal candidiasis were studied: DSY562 was azole susceptible, and DSY565 was isolated after 50 d of fluconazole therapy and was azole resistant.
  • Genomes were sequenced with PacBio RSII and assembled de novo using HGAP3; Illumina paired-end sequencing, RNAseq, Sanger sequencing, MLST, CHEF, and adhesin-prediction pipelines were also used.
  • Genome comparisons used Geneious/Mauve and CLC Genomics Workbench to detect SNPs, indels, rearrangements, shared/unique CDS, introns, and adhesin-like genes.

Limitations

  • The paper states that it cannot yet confirm whether the high adhesin repertoire (>100 genes) is unique to these isolates or shared across *C. glabrata* clades, and it attributes the 101 vs. 107 adhesin difference between DSY562 and DSY565 to technical assembly issues rather than true expansion.
  • The paper states that PacBio misassemblies cannot be excluded for some larger deletions/insertions, especially near chromosome ends and repetitive sequences; homopolymer indels were systematically Sanger-verified, with only 8 of 108 confirmed.
  • The paper notes that only successful clinical progenitors were sampled, which likely underestimates diversity, and that the functional consequences of most nonsynonymous changes remain unclear. Evident from the text: Chr J was incompletely assembled in DSY565, and small contigs enriched in adhesin genes could not be mapped to chromosomes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1534/g3.117.042887

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 42 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    65 CDS from CBS138 were not detected in DSY562 and DSY565.

    “65 CDS from CBS138 were not detected in DSY562 and DSY565 (Figure 3 and File S3).”
    Quote in the paperSubstantial claim
  • Findingown data

    The left arms of Chr L and C were inverted as compared to CBS138.

    “The left arms of Chr L and C were inverted as compared to CBS138.”
    Quote in the paperSubstantial claim
  • Findingown data

    Nuclear and mitochondrial genomes diverged by 0.7% between DSY562 and CBS138.

    “Nuclear and mitochondrial genomes diverged by 0.7% between the two strains.”
    Quote in the paperSubstantial claim
  • Findingown data

    The number of CDS in mitochondrial DNA and the numbers of tRNA were identical between DSY562, DSY565, and CBS138.

    “Table 4 indicates that the number of CDS in mitochondrial DNA and numbers of tRNA were identical between strains.”
    Quote in the paperNot a substantial claim
  • Findingown data

    The CHEF analysis yielded an R2 value of 0.981 when plotting relative migration distance of known CBS138 chromosome sizes against obtained DSY562 and DSY565 chromosome sizes.

    “Plotting the relative migration distance (Rf values) of known CBS138 chromosome sizes with the obtained sizes of DSY562 and DSY565 chromosomes yielded an R2 value of 0.981.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 48
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 12

  • May combine two claims.

    Findingown data

    DSY562 and DSY565 genomes possessed at least 144 intron-containing genes, close to the 150 identified in CBS130.

    “Table 5 shows that DSY562 and DSY565 genomes possessed at least 144 intron-containing genes, which is close to the number identified in CBS130 (150).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Chr A, B, E, G, H, and K kept similar structures between DSY562 and CBS138, while other chromosomes underwent several modifications.

    “While Chr A, B, E, G, H, and K kept similar structures between both strains, other chromosomes underwent several modifications.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    B1J91/B1J92_C02343g (ARB1) contains an intron in CBS138 but lacks a reading frame in DSY562 and DSY565; removal of the intron restores a truncated CDS compared to CBS138.

    “B1J91/B1J92_C02343g (ARB1: a protein with ATPase activity and a role in cellular response to drugs, a ribosomal small subunit exported from the nucleus and cytosol), which contains an intron in CBS138, lacks a reading frame in DSY562 and DSY565. Removal of the intron in this gene restores a truncated CDS as compared to CBS138.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Candida glabrata DSY562 and DSY565 are paired clinical isolates that were isolated from an HIV-positive patient presenting oropharyngeal candidiasis.

    “C. glabrata DSY562 and DSY565 are paired clinical isolates that were isolated from an HIV-positive patient presenting oropharyngeal candidiasis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    B1J91/B1J92_H04257g and B1J91/B1J92_H04279g were found in four tandem repeats on Chr H in DSY562 and DSY565, whereas CBS138 has only one repeat.

    “Interestingly, B1J91/B1J92_H04257g and B1J91/B1J92_H04279g were found in four tandem repeats on Chr H as opposed to CBS138, in which only one repeat is found.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Comparison between DSY562 and DSY565 yielded 17 nonsynonymous SNPs, including the expected PDR1 mutation, and 11 small size indels in coding regions, mainly in adhesin-like genes.

    “Comparison between DSY562 and DSY565 yielded 17 nonsynonymous SNPs (among which the was the expected PDR1 mutation) as well as small size indels in coding regions (11) but mainly in adhesin-like genes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    DSY562 and DSY565 each contained a large set of adhesin-like genes (101 and 107, respectively), exceeding the 63 reported adhesins in the CBS138 genome.

    “DSY562 and DSY565 each contained a large set of adhesin-like genes (101 and 107, respectively), which exceed by far the number of reported adhesins (63) in the CBS138 genome.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites de Groot et al. 2013 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Illumina reads of DSY562 and DSY565 aligned to the CBS138 genome at approximately 95%, with coverage of 72-fold and 64-fold, respectively.

    “In both cases, ∼95% of reads aligned to the CBS genomes and coverage was 72- to 64-fold for DSY562 and DSY565 data, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    B1J91/B1J92_M05687g (NPY1), B1J91/B1J92_G03487g (TMN3), B1J91/B1J92_I10725g (YGR122W), B1J91/B1J92_E01155g (RPA14), and B1J91/B1J92_H06017g (FLR1) exhibit N-terminal truncated proteins as compared to CBS138.

    “B1J91/B1J92_M05687g (NPY1: has NAD+ diphosphatase activity and a role in the NADH metabolic process), B1J91/B1J92_G03487g (TMN3: has a role in cellular copper ion homeostasis), B1J91/B1J92_I10725g (YGR122W: has a role in negative regulation of transcription from the RNA polymerase II promoter), B1J91/B1J92_E01155g (RPA14: RNA polymerase I activity), and B1J91/B1J92_H06017g (FLR1: a multidrug tran”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Parts of Chr L and I were added to Chr F, renamed Chr F-L-I, in DSY562, yielding the largest chromosome in this species at 1.59 Mb.

    “Parts of Chr L and I were added to Chr F (which was renamed as Chr F-L-I) in DSY562, thus yielding the largest chromosome in this species (1.59 Mb).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The 65 CBS138-specific genes included, among others, 6 adhesin-like genes, CAGL0B01243g (MATα1), and CAGL0G07175g, an RNA binding protein with RNA-directed DNA polymerase activity.

    “Genes that were CBS138 specific (65) included, among others, adhesin-like genes (6), CAGL0B01243g (MATα1), and CAGL0G07175g (RNA binding protein with RNA-directed DNA polymerase activity).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Members of the EPA family (19) in DSY562 were well discerned in the phylogenetic tree and harbor typical EPA adhesin signatures, including a PA14 domain and EPA-specific domains, except B1J91_K00170g4.

    “Members of the EPA family (19) were well discerned in this tree (blue color of Figure 5) and harbor typical signatures of EPA adhesins, including a PA14 domain as well as EPA-specific domains (see details in Material and Methods), with the exception of B1J91_K00170g4.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The separate DSY565 assembly yielded the same chromosome arrangement as DSY562, except that Chr J was not completely assembled and was split into Chr J1 and J2.

    “Remarkably, the separate DSY565 assembly yielded the same chromosome arrangement as DSY562, with the exception that Chr J was not completely assembled in DSY565. This chromosome was still split in two parts (Chr J1 and J2; see Table 4 and Figure S1) in DSY565.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PacBio sequencing yielded 14 major contigs and mitochondrial genomes from both DSY562 and DSY565 that were highly similar to each other.

    “The PacBio technology used here yielded 14 major contigs (sizes 0.18–1.6 Mb) and mitochondrial genomes from both DSY562 and DSY565 isolates that were highly similar to each other.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    78 CDS from DSY562 and DSY565 were not found in CBS138, and 61 of these were common to DSY562 and DSY565.

    “78 CDS from DSY562 and DSY565 were not found in CBS138. From these 78 CDS, 61 were common to DSY562 and DSY565; thus highlighting unique CDS for each of the strains.”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    DSY562 and DSY565 both belong to sequence type ST8.

    “DSY562 | ST8 | 4 | 0.25 | 0.5 | — | —”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    rDNAs were identified in DSY562 and DSY565 and were located at the telomeric ends of Chr L and M-J as in CBS138.

    “rDNAs were identified in DSY562 and DSY565, and were located at the telomeric ends of Chr L and M-J as in CBS138.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    There are approximately 370,000 nucleotide differences between the CBS138 and DSY562 genomes, with DSY562 having the largest genome.

    “It is interesting to observe that there are ∼370000 nt differences between the CBS138 and DSY562 genomes (the latter having the largest genome), thus highlighting that additional/novel genes may be present in the DSY strains (see below).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The difference in nucleotide counts for major contigs including mitochondrial DNA is larger (58,400 nucleotides), compensated by nucleotide counts of small contigs that could not be consistently assembled to larger contigs.

    “The difference in nucleotide counts for major contigs (including mitochondrial DNA) is larger (58,400 nucleotides), however this is compensated for by nucleotide counts of the small contigs which could not be consistently assembled to larger contigs.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Comparisons of the clinical genomes with the published CBS138 genome indicated important genome rearrangements, but not between the clinical strains.

    “Comparisons of the clinical genomes with the published CBS138 genome indicated important genome rearrangements, but not between the clinical strains.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Illumina comparisons of DSY562 and DSY565 with CBS138 yielded 85,711-85,986 changes including SNPs and indels and approximately 10,390 nonsynonymous changes.

    “Both comparisons yielded a high number of changes (85,711–85,986 including SNPs and indels) and resulted in ∼10,390 nonsynonymous changes as compared to CBS138.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PacBio major assembled contigs larger than 20 kb numbered 14 for DSY562 and 15 for DSY565, with N50s of 1.06 and 1.17 Mb.

    “As summarized in this table, the number of major assembled contigs (size >20 kb) were 14 and 15 for DSY562 and DSY565, respectively. N50s were 1.06 and 1.17 Mb for both isolates, thus highlighting the high quality of the assemblies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    DSY565 was isolated after 50 days of fluconazole therapy and exhibited azole resistance.

    “DSY565 was isolated after 50 d of fluconazole therapy and exhibited azole resistance (Sanglard et al. 1999) (Table 1).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Sanglard et al. 1999 source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    DSY562 and DSY565 accounted for totals of 12,729,188 and 12,728,164 nucleotides, a difference of 1024 nucleotides between the two genomes.

    “DSY562 and DSY565 accounted for totals of 12,729,188 and 12,728,164 nucleotides. This represents a difference of 1024 nucleotides between the two genomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Tpk5-2 and Tpk5-5 to -9 encoded the same proteins, while Tpk5-3 and -4 were different (66% identity) but still similar to the Tkp5 protein from V. polyspora.

    “We observed that, while Tpk5-2 and Tpk5-5 to -9 encoded the same proteins, Tpk5-3 and -4 were different (66% identity) but still similar to the Tkp5 protein from V. polyspora.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A tandem repeat of B1J91_C01067g is present in DSY562 at the Chr C extremity, while only one copy remained in DSY565.

    “While a tandem repeat of B1J91_C01067g is present in DSY562 at the Chr C extremity, only one copy remained in DSY565.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Chr D-L and Chr L inversions, as well as Chr I-L-D, are among common chromosome patterns, while Chr F-L-I and Chr C inversions seem unique to DSY562 and DSY565.

    “While Chr D-L and Chr L inversions, as well as Chr I-L-D are among the common patterns, Chr F-L-I and Chr C inversions seem unique to DSY562 and DSY565.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Carreté et al. 2017

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    We determined the presence of >100 adhesin-like genes in both DSY strains, which was not yet anticipated from other genome-wide studies.

    “We determined the presence of >100 adhesin-like genes in both DSY strains, which was not yet anticipated from other genome-wide studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    CBS138 and CCTCC M202019 do not exhibit MSH2 defects and they contain a limited repertoire of adhesins as compared to DSY562/DSY565.

    “In agreement with our hypothesis, it is interesting to mention that CBS138 and CCTCC M202019 do not exhibit MSH2 defects and they contain a limited repertoire of adhesins as compared to DSY562/DSY565.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Xu et al. 2016

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Only eight of the 108 putative homopolymeric indels were confirmed by Sanger sequencing; 95 out of 108 were corrected.

    “Only eight of these indels were confirmed by this approach (95 out of 108 were corrected; see Table 6 and File S7).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: PacBio sequencing can yield indel differences in homopolymeric sequences.

  • May combine two claims.

    Findingown data

    Tpk5-1 was located next to B1J91/B1J92_M05115g on Chr G, which is described as similar to Ty5-6, a S. paradoxus retrotransposon; both genes are flanked by the same LTR.

    “Curiously, Tpk5-1 was located next to B1J91/B1J92_M05115g on Chr G, which is described as similar to Ty5-6, a S. paradoxus retrotransposon. Both genes are flanked by the same LTR.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The data suggest that 61 novel adhesin-like proteins were assigned to DSY562, while 40 remained in common with CBS138, considering only 50 adhesin-like proteins without frameshifts.

    “Taken together, the data suggest that 61 novel adhesin-like proteins were assigned to DSY562, while 40 remained in common with CBS138 (Figure 5, only 50 adhesin-like proteins without frameshifts were taken into account in these calculations).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    These reads produced small contigs, as illustrated in Figure S1, which are enriched in adhesin genes.

    “These reads produced small contigs, as illustrated in Figure S1, which are enriched in adhesin genes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Tpk5-2 and Tpk5-5 to -9 were flanked by the same LTRs, while Tpk5-3 and -4 were flanked by other distinct LTRs.

    “As expected from retrotransposons, Tpk5-2 and Tpk5-5 to -9 were flanked by the same LTRs, while Tpk5-3 and -4 were flanked by other distinct LTRs.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    101 adhesin-like genes were identified in DSY562 and 107 in DSY565.

    “While 101 adhesin-like genes were identified in DSY562, 107 adhesin-like genes were found in DSY565 (Figure S1).”
    • Also stated in: § Discussion · plain
      “The number of identified adhesins between both isolates differs substantially (101 in DSY562 vs. 107 in DSY565).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The overlay between both groupings showed consistently that cluster I contained the EPA-like genes and that clusters V and VII and clusters II and III were grouped in two categories that include VSHIT-containing adhesins.

    “The overlay between both grouping showed consistently that cluster I contained the EPA-like genes and that clusters V and VII and clusters II and III were grouped in two categories that include VSHIT-containing adhesins.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The other clusters (IV and VI) are located in distinct branches, the latter being grouped in genes lacking EPA and VSHIT signatures.

    “The other clusters (IV and VI) are located in distinct branches, the latter being grouped in genes lacking EPA and VSHIT signatures.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    Specific mutations in the transcriptional regulator PDR1 result in upregulation of multidrug efflux transporters in Candida glabrata.

    “Specific mutations in the transcriptional regulator PDR1 result in upregulation of the transporters.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida glabrata azole resistance is coupled with selective fitness advantages in animal models of infection.

    “We have shown in the past years that C. glabrata azole resistance is coupled with selective fitness advantages in animal models of infection (Ferrari et al. 2009; Vale-Silva et al. 2013).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Ferrari et al. 2009

      Not checked in the free run.

    • cites Vale-Silva et al. 2013 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    When EPA1 is upregulated, Candida glabrata exhibits increased adherence to host cells, which contributes to enhanced virulence of this yeast species.

    “When EPA1 is upregulated, the consequence is that C. glabrata exhibits increased adherence to host cells, which is one of the factors that contributes to enhance virulence of this yeast species which develops azole resistance (Vale-Silva et al. 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Vale-Silva et al. 2016

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida glabrata can exhibit high mutation rates in the presence of antifungal agents, based on decreased activity of the DNA repair machinery in specific clinical isolates.

    “It has been shown recently that C. glabrata can exhibit high mutation rates in the presence of antifungal agents. This property is based on the decreased activity of the DNA repair machinery that exists in specific clinical isolates (Healey et al. 2016b).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Healey et al. 2016b

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The identified changes do not reflect PacBio errors because the DSY562 and DSY565 assemblies were produced independently and produced the same changes compared to CBS138, and Sanger sequencing confirmed the absence of PacBio errors.

    “We believe that these changes do not reflect PacBio errors since (i) the DSY562 and DSY565 assemblies were produced independently to produce the same changes as compared to CBS138, and (ii) Sanger sequencing verifications confirmed the absence of PacBio errors [see example of B1J91/B1J92_H06017g (FLR1) sequencing in Figure S2].”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data

    Additional or novel genes may be present in the DSY strains.

    “It is interesting to observe that there are ∼370000 nt differences between the CBS138 and DSY562 genomes (the latter having the largest genome), thus highlighting that additional/novel genes may be present in the DSY strains (see below).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The discrepancy of Chr K from DSY562 from expected CBS138 patterns may be due to intrinsic chromosome size variations observed by others for this type of strain.

    “Chr K from DSY562 showed a discrepancy from the expected patterns from CBS138, however this result may be due to intrinsic chromosome size variations observed by others for this type of strain (Bader et al. 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bader et al. 2012

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Another homolog, B1J91/B1J92_A01221g, is present in DSY562 and DSY565 and likely compensates for the probable loss of function of B1J91/B1J92_D00154g.

    “Interestingly, another homolog is present in DSY562 and DSY565 (B1J91/B1J92_A01221g), thus likely compensating for the probable loss of function of B1J91/B1J92_D00154g.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Candida glabrata azole resistance is mediated principally by efflux-dependent mechanisms, while candin resistance is the consequence of mutations in FKS1 and FKS2 encoding the candin target enzyme beta-glucan synthase.

    “While C. glabrata azole resistance is mediated principally by efflux-dependent mechanisms, candin resistance is the consequence of mutations in the genes (FKS1 and FKS2) encoding the candin target enzyme (β-glucan synthase) (Perlin 2015; Vale-Silva and Sanglard 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Perlin 2015

      Not checked in the free run.

    • cites Vale-Silva and Sanglard 2015

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The data indicate extensive divergence between the DSY562 and CBS138 genomes, in general agreement with analyses from other Candida glabrata genomes.

    “These data indicate extensive divergence between the two genomes, however they are in general agreement with the analysis deduced from other C. glabrata genomes (Singh-Babak et al. 2012).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Singh-Babak et al. 2012 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Candida glabrata contains 63 ORFs with adhesin properties.

    “It is estimated that C. glabrata contains 63 ORFs with adhesin properties (de Groot et al. 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites de Groot et al. 2013 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    A PCR-based approach confirmed the absence of Tkp5-7 in DSY565 while leaving the LTR signature.

    “A PCR-based approach confirmed the absence of Tkp5-7 in DSY565 while leaving the LTR signature (see Figure S3).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The mismatch-repair gene MSH2 can modulate drug resistance when its activity is compromised by specific SNPs, giving rise to a hyper-mutator phenotype.

    “It has been reported earlier that the mismatch-repair gene MSH2 can modulate drug resistance when its activity is compromised by specific SNPs, giving rise to a hyper-mutator phenotype (Healey et al. 2016b).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Healey et al. 2016b

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    These features suggest that DSY562 and DSY565 have acquired retrotransposons from different sources and that these strains have undergone several transposition events.

    “Taken together, these features suggest that DSY562 and DSY565 have acquired retrotransposons from different sources and that these strains have undergone several transposition events.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The current literature on DNA mismatch-repair defects highlighted that the occurrence of mutations is not random: DNA regions with a greater density of repeats are more mutable in mismatch-repair defective cells.

    “The current literature on the effect of DNA mismatch-repair defects also highlighted that the occurrence of mutations is not random: DNA regions with a greater density of repeats are more mutable in mismatch-repair defective cells (Ma et al. 2012; Lang et al. 2013).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Ma et al. 2012

      Not checked in the free run.

    • cites Lang et al. 2013 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    This number exceeds by far the numbers published for CBS138 (50-66, depending on criteria) and therefore suggests that an expansion of this gene family occurred in our isolates.

    “This number exceeds by far the numbers published for CBS138 (50–66, depending on the criteria used for selection) and therefore suggests that an expansion of this gene family occurred in our isolates.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Binding of C. glabrata to C. albicans hyphae involved the C. albicans Als3 adhesin.

    “Binding of C. glabrata involved the C. albicans Als3 adhesin.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Tati et al. 2016

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    44-50% of investigated isolates (n = 625) were carrying MSH2 defects, which indicates that the MSH2 defect may confer some selective advantage in C. glabrata.

    “It has been observed that 44–50% of investigated isolates (n = 625) were carrying MSH2 defects which thus indicates that the MSH2 defect may confer some selective advantage in C. glabrata (Dellière et al. 2016; Healey et al. 2016a,b).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Dellière et al. 2016 source

      Not checked in the free run.

    • cites Healey et al. 2016a,b

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The absence of B1J91_E00110g1 in DSY565 may be due to incomplete assembly of Chr J1 in this isolate.

    “This may be due to incomplete assembly of Chr J1 in this isolate.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Chromosome ends are recalcitrant to correct assembly and include repetitive sequences.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    It is likely that recombination events in chromosome-end regions may generate variations that could result in a beneficial phenotype for the fungus.

    “It is likely that recombination events in these regions may generate variations which could result in a beneficial phenotype for the fungus.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Chromosome ends are recalcitrant to correct assembly and include repetitive sequences.

  • May combine two claims.

    Premisecitation

    DSY562, the parent of DSY565, was intrinsically highly adherent to host cells even with the lowest EPA1 expression levels compared to other tested strains, with a PDR1 wild-type allele.

    “On the other hand, we observed that DSY562, the parent of DSY565, was intrinsically highly adherent to host cells, even with the lowest EPA1 expression levels as compared to other tested strains. This intrinsically high adherence capacity was observed with a PDR1 wild-type allele (Vale-Silva et al. 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Vale-Silva et al. 2016

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These genes probably form part of chromosomal ends, but remain presently unassembled to major contigs.

    “These genes probably form part of chromosomal ends, but remain presently unassembled to major contigs.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Chromosome ends are recalcitrant to correct assembly and include repetitive sequences.
59 of 59

  • The paper relies on this without support.

    Virulence traits may be multifactorial.

    “Given that virulence traits may be multifactorial, we reasoned that other mutations may contribute to this phenotype.”

  • The paper relies on this without support.

    PacBio sequencing can yield indel differences in homopolymeric sequences.

    “Since it is known that PacBio can yield these differences, we undertook systematic verifications of these sequences by separate Sanger sequencing of small PCR fragments comprising these putative indels.”

  • The paper relies on this without support.

    Chromosome ends are recalcitrant to correct assembly and include repetitive sequences.

    “Some of the affected CDS are located near to chromosome ends, which are known to be recalcitrant to correct assembly and include repetitive sequences.”
3 of 3

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?

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.

  • DNA dilution concentration is inconsistent with mass and volume

    Minor

    Diluting 5 μg of DNA to 150 μl gives about 0.0333 μg/μl, not 30 μg/μl.

    Reported 30 · recomputed 0.033333

  • Uncorrected homopolymer indel count does not match

    Minor

    If 95 of 108 putative indels were corrected, 13 remained, rather than the stated eight confirmed indels.

    Reported 8 · recomputed 13

  • Abstract understates DSY565 major-contig count

    Minor

    The abstract says both isolates yielded 14 major contigs, whereas Table 2 lists 15 for DSY565.

3 of 3

Cites

Flagged first, then by citations

3 of the 58 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Vale-Silva, L., Beaudoing, E., Tran, V. D. T., & Sanglard, D.
Affiliations
  • Institute of Microbiology, University of Lausanne, CH-1011, Switzerland
  • Center for Integrative Genomics, Lausanne Genomic Technologies Facility, CH-1015, Switzerland
  • SIB Swiss Institute of Bioinformatics (CH)
  • Centre Hospitalier Universitaire Vaudois (CH)
Corresponding author
Sanglard, Dominique
ORCID
Venue
G3 Genes|Genomes|Genetics
Publisher
Oxford University Press (OUP)
Published
2017-08-01
Volume
7
Issue
8
Pages
2413-2426
ISSN
2160-1836 (ISSN-L)
DOI
10.1534/g3.117.042887
PMC
PMC5555451
OpenAlex
W2951922435
Semantic Scholar
ac0f3cdd53cc46eb63c428de6dbb9d93f051e6b5
Cited by
61
References
58
Citations by year
2026: 6 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 11 · 2021: 8 · 2020: 4 · 2019: 9 · 2018: 10 · 2017: 1
FWCI
5.05
Type
journal article
Language
en
Open access
Licence
Locations
  • G3 Genes Genomes Genetics (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • SERVAL (Université de Lausanne) (publishedVersion, other-oa)
  • IRIS (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Research Foundation
  • Université de Lausanne
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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
Keywords
antifungal resistance, azole resistance, multidrug efflux transporter, virulence, retrotransposons, hypermutator phenotype, genome rearrangement, clinical isolates, host adaptation, mitochondrial genome
MeSH terms
Fungal Proteins, Humans, Nucleotides, Genetic Variation, Chromosomes, Fungal, Genome, Fungal, Polymorphism, Single Nucleotide, Genomics, Candida glabrata, INDEL Mutation, Molecular Sequence Annotation

About these checks

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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