Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae

Souza, Ana Carolina R.; Fuchs, Beth Burgwyn; Pinhati, Henrique M. S.; Siqueira, Ricardo A.; Hagen, Ferry; Meis, Jacques F.; Mylonakis, Eleftherios; Colombo, Arnaldo L.

doi:10.1128/aac.01177-15

Cited by 121Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Plant Pathogen Control

Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae

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Souza, Ana Carolina R., Fuchs, Beth Burgwyn, Pinhati, Henrique M. S., Siqueira, Ricardo A., Hagen, Ferry, Meis, Jacques F., Mylonakis, Eleftherios, Colombo, Arnaldo L.·2015·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.01177-15PMC PMC4576033

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Abstract

Candida parapsilosis is the main non-albicans Candida species isolated from patients in Latin America. Mutations in the ERG11 gene and overexpression of membrane transporter proteins have been linked to fluconazole resistance. The aim of this study was to evaluate the molecular mechanisms in fluconazole-resistant strains of C. parapsilosis isolated from critically ill patients. The identities of the nine collected C. parapsilosis isolates at the species level were confirmed through molecular identification with a TaqMan qPCR assay. The clonal origin of the strains was checked by microsatellite typing. The Galleria mellonella infection model was used to confirm in vitro resistance. We assessed the presence of ERG11 mutations, as well as the expression of ERG11 and two additional genes that contribute to antifungal resistance (CDR1 and MDR1), by using real-time quantitative PCR. All of the C. parapsilosis (sensu stricto) isolates tested exhibited fluconazole MICs between 8 and 16 μg/ml. The in vitro data were confirmed by the failure of fluconazole in the treatment of G. mellonella infected with fluconazole-resistant strains of C. parapsilosis. Sequencing of the ERG11 gene revealed a common mutation leading to a Y132F amino acid substitution in all of the isolates, a finding consistent with their clonal origin. After fluconazole exposure, overexpression was noted for ERG11, CDR1, and MDR1 in 9/9, 9/9, and 2/9 strains, respectively. We demonstrated that a combination of molecular mechanisms, including the presence of point mutations in the ERG11 gene, overexpression of ERG11, and genes encoding efflux pumps, are involved in fluconazole resistance in C. parapsilosis.

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Resistance to azoles in C. parapsilosis has been attributed to mutations in MRR1 and ERG11 (Y132F alone or with R398I), and overexpression of CDR1, MDR1, and ERG11.
“Resistance to azoles in C. parapsilosis has been attributed to mutations in the transcription factor gene MRR1 [84] and ERG11 (Y132F, either alone or in combination with an R398I) [85,86,87], and overexpression of CDR1, MDR1, and ERG11 [85,86,88].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [85]

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Pappas, P. G., Kauffman, C. A., Andes, D., Benjamin, D. K., Calandra, T. F., Edwards, J. E., Filler, S. G., Fisher, J. F., Kullberg, B.-J., Zeichner, L. O., et al. (2009) · Clinical Infectious Diseases · doi:10.1086/596757 · Cited by 3,191 · see citing works
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Quindós, G. (2014) · Revista Iberoamericana de Micología · doi:10.1016/j.riam.2013.10.001 · Cited by 219 · see citing works
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Pammi, M., Holland, L., Butler, G., Gacser, A., & Bliss, J. M. (2013) · Pediatric Infectious Disease Journal · doi:10.1097/inf.0b013e3182863a1c · Cited by 206 · see citing works
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Moran, G. P., Sanglard, D., Donnelly, S. M., Shanley, D. B., Sullivan, D. J., & Coleman, D. C. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.7.1819 · Cited by 197 · see citing works
Diethylcarbamazine-related antimicrobial activity in Mycobacterium tuberculosis-infected blood
Kitchen, L. W. (1998) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/42.2.241 · Cited by 183 · see citing works
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Sarvikivi, E., Lyytikäinen, O., Soll, D. R., Pujol, C., Pfaller, M. A., Richardson, M. D., Koukila-Kähkölä, P., Luukkainen, P., & Saxén, H. (2005) · Journal of Clinical Microbiology · doi:10.1128/jcm.43.6.2729-2735.2005 · Cited by 177 · see citing works
Brazilian guidelines for the management of candidiasis – a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia, Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical
Colombo, A. L., Guimarães, T., Camargo, L. F. A., Richtmann, R., Queiroz‐Telles, F., Salles, M. J. C., da Cunha, C. A., Shikanai‐Yasuda, M. A., Moretti, M. L., & Nucci, M. (2013) · The Brazilian Journal of Infectious Diseases · doi:10.1016/j.bjid.2013.02.001 · Cited by 157 · see citing works
Self-citation
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Cantón, E., Pemán, J., Quindós, G., Eraso, E., Miranda-Zapico, I., Álvarez, M., Merino, P., Campos-Herrero, M. I., Marco, F., de la Pedrosa, E. G. G., et al. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00466-11 · Cited by 157 · see citing works
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Jiang, C., Dong, D., Yu, B., Cai, G., Wang, X., Ji, Y., & Peng, Y. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dks481 · Cited by 153 · see citing works
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Barchiesi, F., Calabrese, D., Sanglard, D., Falconi Di Francesco, L., Caselli, F., Giannini, D., Giacometti, A., Gavaudan, S., & Scalise, G. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.6.1578-1584.2000 · Cited by 145 · see citing works
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Heilmann, C. J., Schneider, S., Barker, K. S., Rogers, P. D., & Morschhäuser, J. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01102-09 · Cited by 142 · see citing works
Mechanisms of Azole Resistance in a Clinical Isolate of Candida tropicalis
Vandeputte, P., Larcher, G., Bergès, T., Rénier, G., Chabasse, D., & Bouchara, J. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.11.4608-4615.2005 · Cited by 141 · see citing works
Candida tropicalis antifungal cross-resistance is related to different azole target (Erg11p) modifications
Forastiero, A., Mesa-Arango, A. C., Alastruey-Izquierdo, A., Alcazar-Fuoli, L., Bernal-Martinez, L., Pelaez, T., Lopez, J. F., Grimalt, J. O., Gomez-Lopez, A., Cuesta, I., et al. (2013) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00477-13 · Cited by 131 · see citing works
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Goldman, G. H., Ferreira, M. E. D. S., Marques, E. D. R., Savoldi, M., Perlin, D. S., Park, S., Godoy-Martinez, P. C., Goldman, M. H. S., & Colombo, A. L. (2004) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2004.04.009 · Cited by 119 · see citing works
Self-citation
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Hull, C. M., Parker, J. E., Bader, O., Weig, M., Gross, U., Warrilow, A. G. S., Kelly, D. E., & Kelly, S. L. (2012) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.06253-11 · Cited by 113 · see citing works
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Grossman, N. T., Pham, C. D., Cleveland, A. A., & Lockhart, S. R. (2015) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.04613-14 · Cited by 112 · see citing works
MDR1 -Mediated Drug Resistance in Candida dubliniensis
Wirsching, S., Moran, G. P., Sullivan, D. J., Coleman, D. C., & Morschhäuser, J. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.12.3416-3421.2001 · Cited by 91 · see citing works
Regional data analysis of Candida non‐albicans strains collected in United States medical sites over a 6‐year period, 2006–2011
Pfaller, M. A., Jones, R. N., & Castanheira, M. (2014) · Mycoses · doi:10.1111/myc.12206 · Cited by 91 · see citing works
Transcriptional profiling of azole-resistant Candida parapsilosis strains
Silva, A. P., Miranda, I. M., Guida, A., Synnott, J., Rocha, R., Silva, R., Amorim, A., Pina-Vaz, C., Butler, G., & Rodrigues, A. G. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.01127-10 · Cited by 86 · see citing works
Molecular Mechanisms of Fluconazole Resistance in Candida dubliniensis Isolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis
Perea, S. H., Lopez-Ribot, J. L., Wickes, B. L., Kirkpatrick, W. R., Dib, O. P., Bachmann, S. P., Keller, S. M., Martı́nez, M., & Patterson, T. F. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.6.1695-1703.2002 · Cited by 80 · see citing works
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Redding, S. W., Kirkpatrick, W. R., Coco, B. J., Sadkowski, L. C., Fothergill, A. W., Rinaldi, M. G., Eng, T. Y., & Patterson, T. F. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.5.1879-1881.2002 · Cited by 71 · see citing works
Proteomic analysis of experimentally induced azole resistance in Candida glabrata
Rogers, P. D. (2006) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkl221 · Cited by 64 · see citing works
Fluconazole resistance mechanisms inCandida krusei: The contribution of efflux-pumps
Guinea, J., Sánchez-Somolinos, M., Cuevas, Ó., Peláez, T., & Bouza, E. (2006) · Medical Mycology · doi:10.1080/13693780600561544 · Cited by 58 · see citing works
Microsatellite Genotyping Clarified Conspicuous Accumulation of Candida parapsilosis at a Cardiothoracic Surgery Intensive Care Unit
Diab‐Elschahawi, M., Forstner, C., Hagen, F., Meis, J. F. G. M., Lassnigg, A. M., Presterl, E., & Klaassen, C. H. W. (2012) · Journal of Clinical Microbiology · doi:10.1128/jcm.01179-12 · Cited by 57 · see citing works
Self-citation
Antifungal resistance to fluconazole and echinocandins is not emerging in yeast isolates causing fungemia in a Spanish tertiary care center.
Marcos-Zambrano, L. J., Escribano, P., Sánchez, C., Muñoz, P., Bouza, E., & Guinea, J. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02670-14 · Cited by 49 · see citing works
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Moran, G. P., Sullivan, D. J., Morschhäuser, J., & Coleman, D. C. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.9.2829-2841.2002 · Cited by 42 · see citing works
Variation in random amplified polymorphic DNA (RAPD) profiles specific to fluconazole-resistant and -sensitive strains of Candida albicans
Jain, P., Khan, Z. K., Bhattacharya, E., & Ranade, S. A. (2001) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/s0732-8893(01)00292-9 · Cited by 36 · see citing works
Accurate Identification of Candida parapsilosis (Sensu Lato) by Use of Mitochondrial DNA and Real-Time PCR
Souza, A. C. R., Ferreira, R. C., Gonçalves, S. S., Quindós, G., Eraso, E., Bizerra, F. C., Briones, M. R. S., & Colombo, A. L. (2012) · Journal of Clinical Microbiology · doi:10.1128/jcm.00303-12 · Cited by 33 · see citing works
Self-citation
Upregulation of the ERG11 gene in Candida krusei by azoles.
Tavakoli, M., Zaini, F., Kordbacheh, M., Safara, M., Raoofian, R., & Heidari, M. (2010) · Europe PMC (PubMed Central) · Cited by 21 · see citing works
Two missense mutations, E123Q and K151E, identified in the ERG11 allele of an azole-resistant isolate of Candida kefyr recovered from a stem cell transplant patient for acute myeloid leukemia
Couzigou, C., Gabriel, F., Biteau, N., Fitton‐Ouhabi, V., Noël, T., & Accoceberry, I. (2014) · Medical Mycology Case Reports · doi:10.1016/j.mmcr.2014.04.002 · Cited by 10 · see citing works

Flagged first, then by citations

Research works printed but not linked: 4

[27]Pinhati HM, Casulari LA, Bizerra FC, Siqueira RA, Castro FF, Colombo AL. 2013. Outbreak of candidemia due to fluconazole resistant Candida parapsilosis strains in a tertiary care hospital in Brazil, abstr K-1707 Abstr 53th Intersci Conf Antimicrob Agents Chemother. [Google Scholar]
[30]Clinical and Laboratory Standards Institute. 2008. Reference method for broth dilution antifungal susceptibility testing of yeasts, 3rd ed Approved standard M27-A3. CLSI, Wayne, PA. [Google Scholar]
[31]Clinical and Laboratory Standards Institute. 2012. Reference method for broth dilution antifungal susceptibility testing of yeasts. Fourth informational supplement M27-S4. CLSI, Wayne, PA. [Google Scholar]
[57]Souza AC, Fuchs BB, Siqueira RA, Pinhati HM, Mylonakis E, Colombo AL. 2014. Abstr 54th Intersci Conf Antimicrob Agents Chemother, abstr M-1094. [DOI] [PMC free article] [PubMed] [Google Scholar]

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Healey, 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
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
Fungal resistance to echinocandins and the MDR phenomenon in Candida glabrata
Healey, K., & Perlin, D. S. (2018) · doi:10.20944/preprints201808.0306.v1 · Cited by 194 · see citing works
Triazole Evolution of Candida parapsilosis Results in Cross-Resistance to Other Antifungal Drugs, Influences Stress Responses, and Alters Virulence in an Antifungal Drug-Dependent Manner
Papp, C., Bohner, F., Kocsis, K., Varga, M., Szekeres, A., Bodai, L., Willis, J. R., Gabaldón, T., Tóth, R., Nosanchuk, J. D., et al. (2020) · mSphere · doi:10.1128/msphere.00821-20 · Cited by 42 · see citing works
Blood and intra-abdominal Candida spp. from a multicentre study conducted in Madrid using EUCAST: emergence of fluconazole resistance in Candida parapsilosis, low echinocandin resistance and absence of Candida auris
Díaz-García, J., Gómez, A., Machado, M., Alcalá, L., Reigadas, E., Sánchez-Carrillo, C., Pérez-Ayala, A., Gómez-García De La Pedrosa, E., González-Romo, F., Cuétara, M. S., et al. (2022) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkac288 · Cited by 35 · see citing works

Galleria mellonella’nın Bağışıklığı ile İlgili Proteinler ve Peptitler
Küçük, M. E., & Kaplan, A. (2020) · Biyoloji Bilimleri Araştırma Dergisi
Genome Sequence of Galleria mellonella (Greater Wax Moth)
Lange, A., Beier, S., Huson, D. H., et al. (2018) · Genome Announcements · doi:10.1128/genomea.01220-17 · Cited by 102 · see citing works
Анализ и антибактериальная активность фракций гемолимфы иммунизированных личинок Galleria mellonella
Purygin, P. P., Срибная, О. С., & Буряк, А. К. (2010) · Химико-фармацевтический журнал · doi:10.30906/0023-1134-2010-44-1-50-54
Effect of Galleria mellonella larvae preparation and honeybee products on cell cultures
Spiridonov, N. A., Arkhipov, V. V., Narimanov, A. A., et al. (1992) · Comparative Biochemistry and Physiology Part C Comparative Pharmacology · doi:10.1016/0742-8413(92)90065-f · Cited by 4 · see citing works
Anti-Candida Albicans Activity of Fluconazole in Combination with Ethanol in Vitro
He-an, C. (2005) · The Chinese Journal of Dermatovenereology

Authors: Souza, A. C. R., Fuchs, B. B., Pinhati, H. M. S., Siqueira, R. A., Hagen, F., Meis, J. F., Mylonakis, E., & Colombo, A. L.
Affiliations: Universidade Federal de São Paulo (BR)
Brown University (US)
Universidade de Brasília (BR)
Canisius-Wilhelmina Ziekenhuis (NL)
Radboud University Medical Center (NL)
ORCID: Souza, Ana Carolina R.
Fuchs, Beth Burgwyn
Siqueira, Ricardo A.
Hagen, Ferry
Meis, Jacques F.
Mylonakis, Eleftherios
Colombo, Arnaldo L.
Venue: Antimicrobial Agents and Chemotherapy
Publisher: American Society for Microbiology
Published: 2015-10
Volume: 59
Issue: 10
Pages: 6581-6587
ISSN: 0066-4804 (ISSN-L)
1098-6596
DOI: 10.1128/aac.01177-15
PMC: PMC4576033
OpenAlex: W2161253853
Cited by: 121
References: 55
Citations by year: 2026: 5 · 2025: 8 · 2024: 6 · 2023: 10 · 2022: 20 · 2021: 6 · 2020: 14 · 2019: 14 · 2018: 16 · 2017: 15 · 2016: 5 · 2015: 2
FWCI: 9.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Antimicrobial Agents and Chemotherapy (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
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 parapsilosis, fluconazole resistance, ERG11 mutations, efflux pumps, CDR1, MDR1, antifungal resistance mechanisms, Galleria mellonella infection model, clonal origin, microsatellite typing, critically ill patients, non-albicans Candida
MeSH terms: Animals, Antifungal Agents, Candida, Larva, Microbial Sensitivity Tests, Moths, Fluconazole, Drug Resistance, Fungal

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Candida parapsilosis Resistance to Fluconazole: Molecular Mechanisms and In Vivo Impact in Infected Galleria mellonella Larvae

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