Genetic Variation and Antifungal Susceptibility Profile of Candida auris

Mutia Syarifah Adrir, Findra Setianingrum, Robiatul Adawiyah, Ammar Abdurrahman Hasyim, Anna Rozaliyani

Abstract

Candida auris is an invasive yeast that has spread worldwide since it was first identified in Japan in 2009. C.auris has spread through four genetic clades that emerged between 2008 and 2013 and caused nosocomial outbreaks. The mortality rates of C.auris infections vary significantly between regions, ranging from 30 to 60%. C.auris infections can cause fungemia, invasive candidiasis, and spread to various organs. C.auris has a defense mechanism against the innate immune response and virulence factors that are not fully understood. High thermal and salinity tolerance, excretion of protease enzymes, and the ability to form biofilms are the main virulence factors that influence the pathogenicity of C.auris. Due to limited facilities, the diagnosis of C.auris infections is still hampered in some countries. Accurate strain identification methods are essential to prevent the rapid spread of this pathogen. Molecular techniques, including PCR and sequencing of the D1/D2 region of 28s rDNA or internal transcribed spacer using specific primers, are recommended for faster and more accurate identification. Genetic analysis revealed single-nucleotide polymorphisms (SNPs) that differed between clades, especially in the nuclear and mitochondrial genomes. C.auris exhibits high resistance to fluconazole, amphotericin B, and echinocandins, with some strains being resistant to all three. Resistance mechanisms include ERG11 gene mutations, Erg11p overexpression, and efflux pump activity. The rise of multidrug-resistant strains and high genetic variation complicates infection management, requiring heightened attention to prevent further spread.

Keywords

Candida auris, multi-drug resistant, SNPs, virulence

Full Text:

PDF

References

Du H, Bing J, Hu T, Ennis CL, Nobile CJ, Huang G. Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog. 2020 Oct 22;16(10).

Kordalewska M, Perlin DS. Identification of drug resistant candida auris. Vol. 10, Frontiers in Microbiology. Frontiers Media S.A.; 2019.

Rayens E, Norris KA. Prevalence and Healthcare Burden of Fungal Infections in the United States, 2018. Open Forum Infect Dis. 2022 Jan 1;9(1).

Oladele R, Uwanibe JN, Olawoye IB, Ettu AWO, Meis JF, Happi CT. Emergence and Genomic Characterization of Multidrug Resistant Candida auris in Nigeria, West Africa. Journal of Fungi. 2022 Aug 1;8(8).

Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol. 2009;53(1):41–4.

Sharma C, Kadosh D. Perspective on the origin, resistance, and spread of the emerging human fungal pathogen Candida auris. PLoS Pathog. 2023 Mar 1;19(3 March).

Wang Y, Xu J. Associations between Genomic Variants and Antifungal Susceptibilities in the Archived Global Candida auris Population. Journal of Fungi. 2024 Jan 1;10(1).

Lyman M, Forsberg K, Sexton DJ, Chow NA, Lockhart SR, Jackson BR, et al. Worsening Spread of Candida auris in the United States, 2019 to 2021. Ann Intern Med. 2023 Apr 1;176(4):489–95.

Pandya N, Cag Y, Pandak N, Pekok AU, Poojary A, Ayoade F, et al. International multicentre study of candida auris infections. Journal of Fungi. 2021 Oct 1;7(10).

Sanyaolu A, Okorie C, Marinkovic A, Abbasi AF, Prakash S, Mangat J, et al. Candida auris: An Overview of the Emerging Drug-Resistant Fungal Infection. Vol. 54, Infection and Chemotherapy. Korean Society of Infectious Diseases, Korean Society for Antimicrobial Therapy, Korean Society for AIDS; 2022. p. 236–46.

Fasciana T, Cortegiani A, Ippolito M, Giarratano A, Di Quattro O, Lipari D, et al. Candida auris: An overview of how to screen, detect, test and control this emerging pathogen. Vol. 9, Antibiotics. MDPI AG; 2020. p. 1–14.

Rossato L, Simionatto S, Serafini MR, Alves IA. New Technologies to Diagnose and Treat a Multidrug-Resistant Candida auris: A Patent Review. Vol. 187, Mycopathologia. Springer Science and Business Media B.V.; 2022. p. 535–46.

Chakrabarti A, Sood P. On the emergence, spread and resistance of Candida auris: Host, pathogen and environmental tipping points. Vol. 70, Journal of Medical Microbiology. Microbiology Society; 2021.

Abastabar M, Haghani I, Ahangarkani F, Rezai MS, Taghizadeh Armaki M, Roodgari S, et al. Candida auris otomycosis in Iran and review of recent literature. Vol. 62, Mycoses. Blackwell Publishing Ltd; 2019. p. 101–5.

Gómez-Gaviria M, Martínez-álvarez JA, Chávez-Santiago JO, Mora-Montes HM. Candida haemulonii Complex and Candida auris: Biology, Virulence Factors, Immune Response, and Multidrug Resistance. Vol. 16, Infection and Drug Resistance. Dove Medical Press Ltd; 2023. p. 1455–70.

Mohsin J, Weerakoon S, Ahmed S, Puts Y, Al Balushi Z, Meis JF, et al. A cluster of Candida Auris blood stream infections in a tertiary care hospital in Oman from 2016 to 2019. Antibiotics. 2020 Oct 1;9(10):1–11.

Allert S, Schulz D, Kämmer P, Großmann P, Wolf T, Schäuble S, et al. From environmental adaptation to host survival: Attributes that mediate pathogenicity of Candida auris. Virulence. 2022;13(1):191–214.

Watkins RR, Gowen R, Lionakis MS, Ghannoum M. Update on the Pathogenesis, Virulence, and Treatment of Candida auris. Pathog Immun. 2022;7(2):46–65.

Kim SH, Iyer KR, Pardeshi L, Muñoz JF, Robbins N, Cuomo CA, et al. Genetic Analysis of Candida auris Implicates Hsp90 in Morphogenesis and Azole Tolerance and Cdr1 in Azole Resistance. 2019; Available from: https://doi.org/10.1128/mBio

Chakrabarti A, Singh S. Multidrug-resistant Candida auris: an epidemiological review. Vol. 18, Expert Review of Anti-Infective Therapy. Taylor and Francis Ltd; 2020. p. 551–62.

Ciurea CN, Delia Mare A, Kosovski IB, Toma F, Vintilă C, Man A. Review Candida auris and other phylogenetically related species-a mini-review of the literature [Internet]. 2021. Available from: www.germs.ro

Rossato L, Colombo AL. Candida auris: What have we learned about its mechanisms of pathogenicity? Vol. 9, Frontiers in Microbiology. Frontiers Media S.A.; 2018.

Wang X, Bing J, Zheng Q, Zhang F, Liu J, Yue H, et al. The first isolate of Candida auris in China: Clinical and biological aspects article. Emerg Microbes Infect. 2018 Dec 1;7(1).

Heaney H, Laing J, Paterson L, Walker AW, Gow NAR, Johnson EM, et al. The environmental stress sensitivities of pathogenic candida species, including candida auris, and implications for their spread in the hospital setting. Med Mycol. 2020;58(6):744–55.

de Groot T, Puts Y, Berrio I, Chowdhary A, Meis JF. Development of Candida auris short tandem repeat typing and its application to a global collection of isolates. mBio. 2020 Jan 1;11(1).

Černáková L, Roudbary M, Brás S, Tafaj S, Rodrigues CF. Candida auris: A quick review on identification, current treatments, and challenges. Vol. 22, International Journal of Molecular Sciences. MDPI; 2021.

Kaushik A, Fatima Z, Hameed S. Current Medical Mycology Development of reverse transcription loop-mediated isothermal amplification-based assay for rapid and specific detection of human fungal pathogen, Candida auris. 2024; Available from: https://primerexplorer.jp/lampv5e/index.html

Rhodes J, Fisher MC. Global epidemiology of emerging Candida auris. Vol. 52, Current Opinion in Microbiology. Elsevier Ltd; 2019. p. 84–9.

Kean R, Ramage G. Combined Antifungal Resistance and Biofilm Tolerance: the Global Threat of Candida auris. 2019; Available from: https://doi.org/10.1128/mSphere

Chybowska AD, Childers DS, Farrer RA. Nine Things Genomics Can Tell Us About Candida auris. Vol. 11, Frontiers in Genetics. Frontiers Media S.A.; 2020.

Ahmad S, Asadzadeh M. Strategies to Prevent Transmission of Candida auris in Healthcare Settings. Vol. 17, Current Fungal Infection Reports. Springer; 2023. p. 36–48.

Refbacks

  • There are currently no refbacks.