Investigation of the Physiological, Biochemical and Antifungal Susceptibility Properties of Candida auris

Abstract

Background

Candida auris is an emerging pathogen associated with outbreaks in clinical settings. Isolates of the pathogen have been geographically clustered into four clades with high intra-clade clonality. Pathogenicity varies among the clades, highlighting the importance of understanding these differences.

Objectives

To examine the physiological and biochemical properties of each clade of C. auris to improve our understanding of the fungus.

Methods

Optimal growth temperatures of four strains from three clades, East Asia, South Asia and South Africa, were explored. Moreover, assimilation and antifungal susceptibility properties of 22 C. auris strains from the three clades were studied.

Results

The optimal growth temperatures of all strains were 35–37 °C. Assimilation testing demonstrated that the commercial API ID 32 C system can be used to reliably identify C. auris based on the biochemical properties of the yeast. Notably, C. auris can be uniquely differentiated from commonly clinical fungi by its ability to assimilate raffinose and inability to utilize D-xylose, suggesting a useful simple screening tool. The antifungal susceptibility results revealed that all strains are resistant against fluconazole (minimal inhibitory concentration (MIC) 4 to > 64 µg/mL) and miconazole (MIC 8 to > 16 µg/mL), with strains from the Japanese lineage showing relatively lower MIC values (1–4 µg/mL). Conversely, itraconazole, voriconazole, amphotericin B, micafungin and caspofungin were active against most of the tested strains. On the clade level, East Asian strains generally showed lower MICs against azoles comparing to the other clades, while they displayed MICs against flucytosine higher than those of strains from South Africa and South Asia clades.

Conclusion

Our data suggest a simple identification approach of C. auris based on its physiological and biochemical properties and highlight aspects of C. auris population from various clades.

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References

  1. 1.

    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;53:41–44.

  2. 2.

    Chowdhary A, Sharma C, Duggal S, Agarwal K, Prakash A, Kumar Singh PK, Jain S, Kathuria S, Randhawa HS, Hagen F, Meis JF. New clonal strain of Candida auris, Delhi, India. Emerg Infect Dis. 2013;19:1670–3.

    CAS  Article  Google Scholar 

  3. 3.

    Sarma S, Kumar N, Sharma S, Govil D, Ali T, Mehta Y, Rattan A. Candidemia caused by amphotericin B and fluconazole resistant Candida auris. Indian J Med Microbiol. 2013;31:90–1.

    CAS  Article  Google Scholar 

  4. 4.

    Chowdhary A, Anil Kumar V, Sharma C, Prakash A, Agarwal K, Babu R, Dinesh KR, Karim S, Singh SK, Hagen F, Meis JF. Multidrug-resistant endemic clonal strain of Candida auris in India. Eur J Clin Microbiol Infect Dis. 2014;33:919–26.

    CAS  Article  Google Scholar 

  5. 5.

    Magobo RE, Corcoran C, Seetharam S, Govender NP. Candida auris-associated candidemia. South Africa Emerg Infect Dis. 2014;20:1250–1.

    PubMed  Google Scholar 

  6. 6.

    Calvo B, Melo AS, Perozo-Mena A, Hernandez M, Francisco EC, Hagen F, Meis JF, Colombo AL. First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia. J Infect. 2016;73:369–74.

    Article  Google Scholar 

  7. 7.

    Borman AM, Szekely A, Johnson EM. Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida species. mSphere. 2016;1:e00189–16.

  8. 8.

    Borman AM, Szekely A, Johnson EM. Isolates of the emerging pathogen Candida auris present in the UK have several geographic origins. Med Mycol. 2017;55:563–7.

    CAS  Article  Google Scholar 

  9. 9.

    Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A, Ryan L, Shackleton J, Trimlett R, Meis JF, Armstrong-James D, Fisher MC. First hospital outbreak of the globally emerging Candida auris in a European hospital. Antimicrob Resist Infect Control. 2016;5:35.

    Article  Google Scholar 

  10. 10.

    Govender NP, Magobo RE, Mpembe R, Mhlanga M, Matlapeng P, Corcoran C, Govind C, Lowman W, Senekal M, Thomas J. Candida auris in South Africa, 2012–2016. Emerg Infect Dis. 2018;24:2036–40.

    Article  Google Scholar 

  11. 11.

    Tsay S, Kallen A, Jackson BR, Chiller TM, Vallabhaneni S. Approach to the investigation and management of patients with Candida auris, an emerging multidrug-resistant yeast. Clin Infect Dis. 2018;66:306–11.

    Article  Google Scholar 

  12. 12.

    Welsh RM, Bentz ML, Shams A, Houston H, Lyons A, Rose LJ, Litvintseva AP. Survival, persistence, and isolation of the emerging multidrug-resistant pathogenic yeast Candida auris on a plastic health care surface. J Clin Microbiol. 2017;55:2996–3005.

    CAS  Article  Google Scholar 

  13. 13.

    Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clin Infect Dis. 2017;64:134–40.

    CAS  Article  Google Scholar 

  14. 14.

    Chow NA, de Groot T, Badali H, Abastabar M, Chiller TM, Meis JF. Potential fifth clade of Candida auris, Iran, 2018. Emerg Infect Dis. 2019;25:1780–1.

    Article  Google Scholar 

  15. 15.

    Kwon YJ, Shin JH, Byun SA, Choi MJ, Won EJ, Lee D, Lee SY, Chun S, Lee JH, Choi HJ, Kee SJ, Kim SH, Shin MG. Candida auris clinical isolates from South Korea: identification, antifungal susceptibility, and genotyping. J Clin Microbiol. 2019;57:e01624-e1718.

    CAS  Article  Google Scholar 

  16. 16.

    Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH, Jang HC. First three reported cases of nosocomial fungemia caused by Candida auris. J Clin Microbiol. 2011;49:3139–42.

    CAS  Article  Google Scholar 

  17. 17.

    Mizusawa M, Miller H, Green R, Lee R, Durante M, Perkins R, Hewitt C, Simner PJ, Carroll KC, Hayden RT, Zhang SX. Can multidrug-resistant Candida auris be reliably identified in clinical microbiology laboratories? J Clin Microbiol. 2017;55:638–40.

    Article  Google Scholar 

  18. 18.

    Kathuria S, Singh PK, Sharma C, Prakash A, Masih A, Kumar A, Meis JF, Chowdhary A. Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization–time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by Vitek 2, CLSI broth microdilution, and Etest method. J Clin Microbiol. 2015;53:1823–30.

    CAS  Article  Google Scholar 

  19. 19.

    Kordalewska M, Zhao Y, Lockhart SR, Chowdhary A, Berrio I, Perlin DS. Rapid and accurate molecular identification of the emerging multidrug-resistant pathogen Candida auris. J Clin Microbiol. 2017;55:2445–52.

    CAS  Article  Google Scholar 

  20. 20.

    Leach L, Zhu Y, Chaturvedi S. Development and validation of a real-time PCR assay for rapid detection of Candida auris from surveillance samples. J Clin Microbiol. 2018;56:e01223-e1317.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Yamamoto M, Alshahni MM, Tamura T, Satoh K, Iguchi S, Kikuchi K, Mimaki M, Makimura K. Rapid detection of Candida auris based on loop-mediated isothermal amplification (LAMP). J Clin Microbiol. 2018;56:e00591-e618.

    CAS  Article  Google Scholar 

  22. 22.

    Vatanshenassan M, Boekhout T, Mauder N, Robert V, Maier T, Meis JF, Berman J, Then E, Kostrzewa M, Hagen F. Evaluation of microsatellite typing, ITS sequencing, AFLP fingerprinting, MALDI-TOF MS, and Fourier-transform infrared spectroscopy analysis of Candida auris. J Fungi (Basel). 2020;6:146.

    Article  Google Scholar 

  23. 23.

    Forgács L, Borman AM, Prépost E, Tóth Z, Kardos G, Kovács R, Szekely A, Nagy F, Kovacs I, Majoros L. Comparison of in vivo pathogenicity of four Candida auris clades in a neutropenic bloodstream infection murine model. Emerg Microbes Infect. 2020;9:1160–9.

    Article  Google Scholar 

  24. 24.

    APIWEBTM. https://apiweb.biomerieux.com/login. Accessed 1 June 2020.

  25. 25.

    Lapage SP, Bascomb S, Willcox WR, Curtis MA. Identification of bacteria by computer: general aspects and perspectives. J Gen Microbiol. 1973;77:273–90.

    CAS  Article  Google Scholar 

  26. 26.

    Centers for Disease Control and Prevention. Identification of Candida auris. https://www.cdc.gov/fungal/candida-auris/identification.html. Accessed 24 June 2020.

  27. 27.

    Cendejas-Bueno E, Kolecka A, Alastruey-Izquierdo A, Theelen B, Groenewald M, Kostrzewa M, Cuenca-Estrella M, Gómez-López A, Boekhout T. Reclassification of the Candida haemulonii complex as Candida haemulonii (C. haemulonii group I), C. duobushaemulonii sp. nov. (C. haemulonii group II), and C. haemulonii var. vulnera var. nov.: three multiresistant human pathogenic yeasts. J Clin Microbiol. 2012;50:3641–51.

    CAS  Article  Google Scholar 

  28. 28.

    Rhodes J, Abdolrasouli A, Farrer RA, Cuomo CA, Aanensen DM, Armstrong-James D, Fisher MC, Schelenz S. Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris. Emerg Microbes Infect. 2018;7:1–12.

    CAS  Google Scholar 

  29. 29.

    Eyre DW, Sheppard AE, Madder H, Moir I, Moroney R, Quan TP, Griffiths D, George S, Butcher L, Morgan M, Newnham R, Sunderland M, Clarke T, Foster D, Hoffman P, Borman AM, Johnson EM, Moore G, Brown CS, Walker AS, Peto TEA, Crook DW, Jeffery KJM. A Candida auris outbreak and its control in an intensive care setting. N Engl J Med. 2018;379:1322–31.

    Article  Google Scholar 

  30. 30.

    Szekely A, Borman AM, Johnson EM. Candida auris isolates of the Southern Asian and South African lineages exhibit different phenotypic and antifungal susceptibility profiles In Vitro. J Clin Microbiol. 2019;57:e02055-e2118.

    CAS  Article  Google Scholar 

  31. 31.

    Köhler JR, Hube B, Puccia R, Casadevall A, Perfect JR. Fungi that infect humans. Microbiol Spectr. 2017;5(3).

  32. 32.

    Ghosh AK, Paul S, Sood P, Rudramurthy SM, Rajbanshi A, Jillwin TJ, Chakrabarti A. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for the rapid identification of yeasts causing bloodstream infections. Clin Microbiol Infect. 2015;21:372–8.

    CAS  Article  Google Scholar 

  33. 33.

    Girard V, Mailler S, Chetry M, Vidal C, Durand G, van Belkum A, Colombo AL, Hagen F, Meis JF, Chowdhary A. Identification and typing of the emerging pathogen Candida auris by matrix-assisted laser desorption ionisation time of flight mass spectrometry. Mycoses. 2016;59:535–8.

    CAS  Article  Google Scholar 

  34. 34.

    Wickerhan LJ, Burton KA. Carbon assimilation tests for the classification of yeasts. J Bacteriol. 1948;56:363–71.

    CAS  Article  Google Scholar 

  35. 35.

    Bowman PI, Ahearn DG. Evaluation of commercial systems for the identification of clinical yeast isolates. J Clin Microbiol. 1976;4:49–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Bergan T, Hollum AB, Vangdal M. Evaluation of four commercial biochemical test systems for identification of yeasts. Eur J Clin Microbiol. 1982;1:217–22.

    CAS  Article  Google Scholar 

  37. 37.

    Larkin E, Hager C, Chandra J, Mukherjee PK, Retuerto M, Salem I, Long L, Isham N, Kovanda L, Borroto-Esoda K, Wring S, Angulo D, Ghannoum M. The emerging pathogen Candida auris: growth phenotype, virulence factors, activity of antifungals, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation. Antimicrob Agents Chemother. 2017;61:e02396-e2416.

    CAS  Article  Google Scholar 

  38. 38.

    Wanger A, Mills K, Nelson PW, Rex JH. Comparison of Etest and National Committee for Clinical Laboratory Standards broth macrodilution method for antifungal susceptibility testing: enhanced ability to detect amphotericin B-resistant Candida isolates. Antimicrob Agents Chemother. 1995;39:2520–2.

    CAS  Article  Google Scholar 

  39. 39.

    Flowers SA, Colon B, Whaley SG, Schuler MA, Rogers PD. Contribution of clinically derived mutations in ERG11 to azole resistance in Candida albicans. Antimicrob Agents Chemother. 2015;59:450–60.

    Article  Google Scholar 

  40. 40.

    Yurkov AM, Kachalkin AV, Daniel HM, Groenewald M, Libkind D, de Garcia V, Zalar P, Gouliamova DE, Boekhout T, Begerow D. Two yeast species Cystobasidium psychroaquaticum f.a. sp. nov. and Cystobasidium rietchieii f.a. sp. nov. isolated from natural environments, and the transfer of Rhodotorula minuta clade members to the genus Cystobasidium. Antonie Van Leeuwenhoek. 2015;107:173–85.

    CAS  Article  Google Scholar 

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Acknowledgments

The authors express their sincere appreciation for those who have provided some of the fungal strains.

Funding

This work was supported in part by the Emerging/Re-emerging Infectious Disease Project of the Japan Agency for Medical Research and Development, AMED (JP20fk108094).

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Correspondence to Koichi Makimura.

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AMR Mycosis Control Research in the Environment of Treatment and Education for Physically and Mentally Handicapped Persons is an endowed department supported with an unrestricted grant from the Social Welfare Corporation Hirakata Ryoikuen.

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Du, M., Hu, W., Tamura, T. et al. Investigation of the Physiological, Biochemical and Antifungal Susceptibility Properties of Candida auris. Mycopathologia (2021). https://doi.org/10.1007/s11046-020-00526-w

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Keywords

  • Candida auris
  • Identification
  • Assimilation
  • API ID 32 C
  • Susceptibility