MOLECULAR DETERMINANTS OF ANTIFUNGAL RESISTANCE IN CANDIDA AURIS
Keywords:
antifungal resistance, Candida auris, amphotericin B, 5-fluorocytosine, caspofungin, fluconazole.Abstract
Candida auris is known for its strains resistant to multiple antifungal agents, prompting research into the molecular mechanisms underlying this resistance. This review aims to summarize key findings from recent studies. A comprehensive search of online databases and relevant websites was conducted. The analysis reveals that most C. auris strains exhibit high resistance to fluconazole, moderate resistance to amphotericin B, and lower resistance to 5-fluorocytosine and caspofungin. Amphotericin B resistance in C. auris has been linked to the overexpression of mutated ERG genes, resulting in reduced ergosterol levels. Resistance to fluconazole is largely attributed to mutations in the ERG11 gene, an increased number of ERG11 gene copies, and overexpression of efflux pumps. For 5-fluorocytosine, resistance is hypothesized to stem from mutations in the FCY2, FCY1, and FUR1 genes. Caspofungin resistance is associated with mutations in the FKS1 gene. Moreover, resistance to each antifungal appears to be closely related to the clade type of the C. auris strain.
References
Chybowska A.D., Childers D.S., Farrer R.A. Nine Things Genomics Can Tell Us About Candida auris. Front. Genet. 2020;11:351. doi: 10.3389/fgene.2020.00351. [DOI] [PMC free article] [PubMed] [Google Scholar]
Sarma S., Upadhyay S. Current perspective on emergence, diagnosis and drug resistance in Candida auris. Infect. Drug Resist. 2017;10:155–165. doi: 10.2147/IDR.S116229. [DOI] [PMC free article] [PubMed] [Google Scholar]
Parra-Giraldo C.M., Valderrama S.L., Cortes-Fraile G., Garzón J.R., Ariza B.E., Morio F., Linares-Linares M.Y., Ceballos-Garzón A., de la Hoz A., Hernández C., et al. First report of sporadic cases of Candida auris in Colombia. Int. J. Infect. Dis. 2018;69:63–67. doi: 10.1016/j.ijid.2018.01.034. [DOI] [PubMed] [Google Scholar]
Calvo B., Melo A.S., Perozo-Mena A., Hernández M., Francisco E.C., Hagen F., Meis J.F., Lopes Colombo A. First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia. J. Infect. 2016;73:369–374. doi: 10.1016/j.jinf.2016.07.008. [DOI] [PubMed] [Google Scholar]
Chow N.A., Muñoz J.F., Gade L., Berkow E.L., Li X., Welsh R.M., Forsberg K., Lockhart S.R., Adam R., Alanio A., et al. Tracing the evolutionary history and global expansion of Candida auris using population genomic analyses. mBio. 2020;11:e03364-19. doi: 10.1128/mBio.03364-19. [DOI] [PMC free article] [PubMed] [Google Scholar]
Lockhart S.R., Etienne K.A., Vallabhaneni S., Farooqi J., Chowdhary A., Govender N.P., Lopes Colombo A., Calvo B., Cuomo C.A., Desjardins C.A. Simultaneous emergence of multidrug resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin. Infect. Dis. 2017;64:134–140. doi: 10.1093/cid/ciw691. [DOI] [PMC free article] [PubMed] [Google Scholar]
Escandón 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. Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization with Regional Patterns in Amphotericin B Resistance. Clin. Infect. Dis. 2019;68:15–21. doi: 10.1093/cid/ciy411. [DOI] [PubMed] [Google Scholar]
Rhodes J., Abdolrasouli A., Farrer R.A., Cuomo C.A., Aanensen D.M., Armstrong-James D., Fisher M.C., Schelenz S. Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris. Emerg. Microbes Infect. 2018;7:43. doi: 10.1038/s41426-018-0045-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
Chow N.O., De Groot T., Badali H., Abastabar M., Chiller T.M., Meis J.F. Potential fifth clade of Candida auris, Iran, 2018. Emerg. Infect. Dis. 2019;25:1780–1781. doi: 10.3201/eid2509.190686. [DOI] [PMC free article] [PubMed] [Google Scholar]
Kordalewska M., Lee A., Park S., Berrio I., Chowdhary A., Zhao Y., Perlin D.S. Understanding echinocandin resistance in the emerging pathogen Candida auris. Antimicrob. Agents Chemother. 2018;62:e00238-18. doi: 10.1128/AAC.00238-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
Musayeva, S. I., & Mengliyeva, S. S. (2022). Kursantlarning madaniyatlararo rivojlantirish.
Dal Mas C., Rossato L., Shimizu T., Oliveira E.B., da Silva Junior P.I., Meis J.F., Lopes Colombo A., Hayashi M.A.F. Effects of the natural peptide crotamine from a South American rattlesnake on Candida auris, an emergent multidrug antifungal resistant human pathogen. Biomolecules. 2019;9:205. doi: 10.3390/biom9060205. [DOI] [PMC free article] [PubMed] [Google Scholar]
