DOI QR코드

DOI QR Code

Comprehensive Overview of Candida auris: An Emerging Multidrug-Resistant Fungal Pathogen

  • Ji-Seok Kim (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Hyunjin Cha (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University) ;
  • Yong-Sun Bahn (Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University)
  • 투고 : 2024.04.24
  • 심사 : 2024.06.05
  • 발행 : 2024.07.28

초록

The rise of Candida auris, a multidrug-resistant fungal pathogen, across more than 40 countries, has signaled an alarming threat to global health due to its significant resistance to existing antifungal therapies. Characterized by its rapid spread and robust drug resistance, C. auris presents a critical challenge in managing infections, particularly in healthcare settings. With research on its biological traits and genetic basis of virulence and resistance still in the early stages, there is a pressing need for a concerted effort to understand and counteract this pathogen. This review synthesizes current knowledge on the epidemiology, biology, genetic manipulation, pathogenicity, diagnostics, and resistance mechanisms of C. auris, and discusses future directions in research and therapeutic development. By exploring the complexities surrounding C. auris, we aim to underscore the importance of advancing research to devise effective control and treatment strategies.

키워드

과제정보

This work was supported by National Research Foundation of Korea funded by the Korean government (MSIT) (2021R1A2B5B03086596 and 2021M3A9I4021434). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

참고문헌

  1. Denning DW. 2024. Global incidence and mortality of severe fungal disease. Lancet Infect. Dis. 24: 00103-00108.
  2. Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, et al. 2022. Tackling the emerging threat of antifungal resistance to human health. Nat. Rev. Microbiol. 20: 557-571.
  3. Perlin DS, Rautemaa-Richardson R, Alastruey-Izquierdo A. 2017. The global problem of antifungal resistance: prevalence, mechanisms, and management. Lancet Infect. Dis. 17: e383-e392.
  4. Kim MN, Shin JH, Sung H. 2009. Candida haemulonii and closely related species at 5 university hospitals in Korea: identification, antifungal susceptibility, and clinical features. Clin. Infect. Dis. 48: e57-61.
  5. Satoh K, Makimura K, Hasumi Y. 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.
  6. Oh, Bong Joon. 2011. Biofilm formation and genotyping of Candida haemulonii, Candida pseudohaemulonii, and a proposed new species (Candida auris) isolates from Korea. Med. Mycol. 49.1: 98-102.
  7. Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, et cl. 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.
  8. Tharp B, Zheng R, Bryak G, Litvintseva AP, Hayden MK, Chowdhary A, et al. 2023. Role of microbiota in the skin colonization of Candida auris. mSphere 8: e0062322.
  9. Du H, Bing J, Hu T, Ennis CL, Nobile CJ, Huang G. 2020. Candida auris: epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog. 16: e1008921.
  10. Xin H. 2022. Commentary: experimental mouse models of invasive Candidiasis caused by Candida auris and other medically important Candida species. J. Cell Immunol. 4: 29-33.
  11. Cortegiani A, Misseri G, Fasciana T, Giammanco A, Giarratano A, Chowdhary A. 2018. Epidemiology, clinical characteristics, resistance, and treatment of infections by Candida auris. J. Intensive Care 6: 69.
  12. Egger NB, Kainz K, Schulze A, Bauer MA, Madeo F, Carmona-Gutierrez D. 2022. The rise of Candida auris: from unique traits to coinfection potential. Microb. Cell. 9: 141-144.
  13. Shariq A, Rasheed Z, Alghsham RS, Abdulmonem WA. 2023. Candida auris: an emerging fungus that presents a serious global health threat. Int. J. Health Sci. (Qassim) 17: 1-2.
  14. Alfouzan W, Dhar R, Albarrag A, Al-Abdely H. 2019. The emerging pathogen Candida auris: a focus on the Middle-Eastern countries. J. Infect. Public Health 12: 451-459.
  15. Sanyaolu A, Okorie C, Marinkovic A, Abbasi AF, Prakash S, Mangat J, et al. 2022. Candida auris: an overview of the emerging drug-resistant fungal infection. Infect. Chemother. 54: 236-246.
  16. Chow NA, de Groot T, Badali H, Abastabar M, Chiller TM, Meis JF. 2019. Potential fifth clade of Candida auris, Iran, 2018. Emerg. Infect. Dis. 25: 1780-1781.
  17. Desnos-Ollivier M, Fekkar A, Bretagne S. 2021. Earliest case of Candida auris infection imported in 2007 in Europe from India prior to the 2009 description in Japan. J. Mycol. Med. 31: 101139.
  18. Kohlenberg A, Struelens MJ, Monnet DL, Plachouras D, Candida auris survey collaborative g. 2018. Candida auris: epidemiological situation, laboratory capacity and preparedness in European Union and European Economic Area countries, 2013 to 2017. Euro. Surveill. 23: 18-00136.
  19. Ruiz Gaitan AC, Moret A, Lopez Hontangas JL, Molina JM, Aleixandre Lopez AI, Cabezas AH, et al. 2017. Nosocomial fungemia by Candida auris: first four reported cases in continental Europe. Rev. Iberoam. Micol. 34: 23-27.
  20. Rossato L, Colombo AL. 2018. Candida auris: what have we learned about its mechanisms of pathogenicity? Front. Microbiol. 9: 3081.
  21. Borman AM, Szekely A, Johnson EM. 2016. Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida species. mSphere 1: e00189-16.
  22. Singh R, Kaur M, Chakrabarti A, Shankarnarayan SA, Rudramurthy SM. 2019. Biofilm formation by Candida auris isolated from colonising sites and candidemia cases. Mycoses 62: 706-709.
  23. Hernando-Ortiz A, Mateo E, Perez-Rodriguez A, de Groot PWJ, Quindos G, Eraso E. 2021. Virulence of Candida auris from different clinical origins in Caenorhabditis elegans and Galleria mellonella host models. Virulence 12: 1063-1075.
  24. Bravo Ruiz G, Ross ZK, Gow NAR, Lorenz A. 2020. Pseudohyphal growth of the emerging pathogen Candida auris is triggered by genotoxic stress through the S phase checkpoint. mSphere 5: e00151-2.
  25. Wang X, Bing J, Zheng Q, Zhang F, Liu J, Yue H, et al. 2018. The first isolate of Candida auris in China: clinical and biological aspects. Emerg. Microbes Infect. 7: 93.
  26. Grahl N, Demers EG, Crocker AW, Hogan DA. 2017. Use of RNA-protein complexes for genome editing in non-albicans Candida Species. mSphere 2: e00218-00217.
  27. Ennis CL, Hernday AD, Nobile CJ. 2021. A markerless CRISPR-mediated system for genome editing in Candida auris reveals a conserved role for Cas5 in the caspofungin response. Microbiol. Spectr. 9: e0182021.
  28. Gao J, Chow EWL, Wang H, Xu X, Cai C, Song Y, et al. 2021. LncRNA DINOR is a virulence factor and global regulator of stress responses in Candida auris. Nat Microbiol. 6: 842-851.
  29. Defosse TA, Le Govic Y, Vandeputte P, Courdavault V, Clastre M, Bouchara JP, et al. 2018. A synthetic construct for genetic engineering of the emerging pathogenic yeast Candida auris. Plasmid. 95: 7-10.
  30. Santana DJ, O'Meara TR. 2021. Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains. Nat. Commun. 12: 7197.
  31. Bundock P, den Dulk-Ras A, Beijersbergen A, Hooykaas PJ. 1995. Trans-kingdom T-DNA transfer from Agrobacterium tumefaciens to Saccharomyces cerevisiae. EMBO J. 14: 3206-3214.
  32. Munoz JF, Welsh RM, Shea T, Batra D, Gade L, Howard D, et al. 2021. Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in Candida auris. Genetics 218: iyab029.
  33. Kean R, Delaney C, Sherry L, Borman A, Johnson EM, Richardson MD, et al. 2018. Transcriptome assembly and profiling of Candida auris reveals novel insights into biofilm-mediated resistance. mSphere 3: e00334-00318.
  34. Chaffin WL. 2008. Candida albicans cell wall proteins. Microbiol. Mol. Biol. Rev. 72: 495-544.
  35. Polke M, Hube B, Jacobsen ID. 2015. Candida survival strategies. Adv. Appl. Microbiol. 91: 139-235.
  36. Chatterjee S, Alampalli SV, Nageshan RK, Chettiar ST, Joshi S, Tatu US. 2015. Draft genome of a commonly misdiagnosed multidrug resistant pathogen Candida auris. BMC Genomics 16: 686.
  37. Bing J, Wang S, Xu H, Fan S, Du H, Nobile CJ, et al. 2022. A case of Candida auris candidemia in Xiamen, China, and a comparative analysis of clinical isolates in China. Mycology 13: 68-75.
  38. Xin H, Mohiuddin F, Tran J, Adams A, Eberle K. 2019. Experimental mouse models of disseminated Candida auris infection. mSphere 4: e00339-00319.
  39. Garcia-Carnero LC, Clavijo-Giraldo DM, Gomez-Gaviria M, Lozoya-Perez NE, Tamez-Castrellon AK, Lopez-Ramirez LA, et al. 2020. Early virulence predictors during the Candida species-Galleria mellonella interaction. J. Fungi (Basel) 6: 152.
  40. Wurster S, Bandi A, Beyda ND, Albert ND, Raman NM, Raad II, et al. 2019. Drosophila melanogaster as a model to study virulence and azole treatment of the emerging pathogen Candida auris. J. Antimicrob. Chemother. 74: 1904-1910.
  41. Johnson CJ, Davis JM, Huttenlocher A, Kernien JF, Nett JE. 2018. Emerging fungal pathogen Candida auris evades neutrophil attack. mBio 9: e01403-01418.
  42. Thatchanamoorthy N, Rukumani Devi V, Chandramathi S, Tay ST. 2022. Candida auris: a mini review on epidemiology in healthcare facilities in asia. J. Fungi (Basel). 8: 1126.
  43. Vatanshenassan M, Boekhout T, Meis JF, Berman J, Chowdhary A, Ben-Ami R, et al. 2019. Candida auris identification and rapid antifungal susceptibility testing against echinocandins by MALDI-TOF MS. Front. Cell Infect. Microbiol. 9: 20.
  44. Jeffery-Smith A, Taori SK, Schelenz S, Jeffery K, Johnson EM, Borman A, et al. 2018. Candida auris: a review of the literature. Clin. Microbiol. Rev. 31: e00029-00017.
  45. Ahmad S, Alfouzan W. 2021. Candida auris: epidemiology, diagnosis, pathogenesis, antifungal susceptibility, and infection control measures to combat the spread of infections in healthcare facilities. Microorganisms 9: 807.
  46. Kordalewska M, Perlin DS. 2019. Molecular diagnostics in the times of surveillance for Candida auris. J. Fungi (Basel) 5: 77.
  47. Ambaraghassi G, Dufresne PJ, Dufresne SF, Vallieres E, Munoz JF, Cuomo CA, et al. 2019. Identification of Candida auris by use of the updated Vitek 2 Yeast Identification System, Version 8.01: a multilaboratory evaluation study. J. Clin. Microbiol. 57: e00884-00819.
  48. Arendrup MC, Prakash A, Meletiadis J, Sharma C, Chowdhary A. 2017. Comparison of EUCAST and CLSI reference microdilution MICs of eight antifungal compounds for Candida auris and associated tentative epidemiological cutoff values. Antimicrob. Agents Chemother. 61: e00485-00417.
  49. Fasciana T, Cortegiani A, Ippolito M, Giarratano A, Di Quattro O, Lipari D, et al. 2020. Candida auris: an overview of how to screen, detect, test and control this emerging pathogen. Antibiotics (Basel) 9: 778.
  50. Tu J, Liu N, Huang Y, Yang W, Sheng C. 2022. Small molecules for combating multidrug-resistant superbug Candida auris infections. Acta Pharm. Sin B. 12: 4056-4074.
  51. Osset-Trenor P, Pascual-Ahuir A, Proft M. 2023. Fungal drug response and antimicrobial resistance. J. Fungi (Basel) 9: 565.
  52. Vu BG, Moye-Rowley WS. 2022. Azole-resistant alleles of ERG11 in Candida glabrata trigger activation of the Pdr1 and Upc2A transcription factors. Antimicrob. Agents Chemother. 66: e0209821.
  53. Jangir P, Kalra S, Tanwar S, Bari VK. 2023. Azole resistance in Candida auris: mechanisms and combinatorial therapy. APMIS 131: 442-462.
  54. Bhattacharya S, Holowka T, Orner EP, Fries BC. 2019. Gene duplication associated with increased fluconazole tolerance in Candida auris cells of advanced generational age. Sci. Rep. 9: 5052.
  55. Carolus H, Pierson S, Lagrou K, Van Dijck P. 2020. Amphotericin B and other polyenes-discovery, clinical use, mode of action and drug resistance. J. Fungi (Basel). 6: 321.
  56. Rhodes J, Abdolrasouli A, Farrer RA, Cuomo CA, Aanensen DM, Armstrong-James D, et al. 2018. Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris. Emerg. Microbes Infect. 7: 43.
  57. Wasi M, Khandelwal NK, Moorhouse AJ, Nair R, Vishwakarma P, Bravo Ruiz G, et al. 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.
  58. Szymanski M, Chmielewska S, Czyzewska U, Malinowska M, Tylicki A. 2022. Echinocandins - structure, mechanism of action and use in antifungal therapy. J. Enzyme. Inhib. Med. Chem. 37: 876-894.
  59. Trovato L, Bongiorno D, Calvo M, Migliorisi G, Boraccino A, Musso N, et al. 2021. Resistance to echinocandins complicates a case of Candida albicans bloodstream infection: a case report. J. Fungi (Basel) 7: 405.
  60. Lyman M, Forsberg K, Sexton DJ, Chow NA, Lockhart SR, Jackson BR, et al. 2023. Worsening spread of Candida auris in the United States, 2019 to 2021. Ann. Intern. Med. 176: 489-495.
  61. Logan A, Wolfe A, Williamson JC. 2022. Antifungal resistance and the Role of new therapeutic agents. Curr. Infect. Dis. Rep.24: 105-116.
  62. Hager CL, Larkin EL, Long L, Zohra Abidi F, Shaw KJ, Ghannoum MA. 2018. In vitro and in vivo evaluation of the antifungal activity of APX001A/APX001 against Candida auris. Antimicrob. Agents Chemother. 62: e02319-02317.
  63. Ji-Seok Kim K-TL, Yong-Sun Bahn. 2023. Deciphering the regulatory mechanisms of the cAMP/protein kinase A pathway and their roles in the pathogenicity of Candida auris. Microbiol Spectr. 11: e0215223.
  64. Kim JS, Lee KT, Lee MH, Cheong E, Bahn YS. 2021. Adenylyl cyclase and protein kinase A play redundant and distinct roles in growth, differentiation, antifungal drug resistance, and pathogenicity of Candida auris. mBio 12: e0272921.
  65. Day AM, McNiff MM, da Silva Dantas A, Gow NAR, Quinn J. 2018. Hog1 regulates stress tolerance and virulence in the emerging fungal pathogen Candida auris. mSphere 3: e00506-00518.
  66. Horton MV, Johnson CJ, Zarnowski R, Andes BD, Schoen TJ, Kernien JF, et al. 2021. Candida auris cell wall mannosylation contributes to neutrophil evasion through pathways divergent from Candida albicans and Candida glabrata. mSphere 6: e0040621.
  67. Kim JS, Lee KT, Bahn YS. 2023. Secreted aspartyl protease 3 regulated by the Ras/cAMP/PKA pathway promotes the virulence of Candida auris. Front. Cell Infect. Microbiol. 13: 1257897.
  68. Santana DJ, Anku JAE, Zhao G, Zarnowski R, Johnson CJ, Hautau H, et al. 2023. A Candida auris-specific adhesin, Scf1, governs surface association, colonization, and virulence. Science 381: 1461-1467.