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Tools and techniques to identify, study, and control Candida auris

Abstract

Candida auris, is an emerging fungal pathogen that can cause life-threatening infections in humans. Unlike many other Candida species that colonize the intestine, C. auris most efficiently colonizes the skin. Such colonization contaminates the patient’s environment and can result in rapid nosocomial transmission. In addition, this transmission can lead to outbreaks of systemic infections that have mortality rates between 40% and 60%. C. auris isolates resistant to all known classes of antifungals have been identified and as such, understanding the underlying biochemical mechanisms of how skin colonization initiates and progresses is critical to developing better therapeutic options. With this review, we briefly summarize what is known about horizontal transmission and current tools used to identify, understand, and control C. auris infections.

Citation: Carty J, Chowdhary A, Bernstein D, Thangamani S (2023) Tools and techniques to identify, study, and control Candida auris. PLoS Pathog 19(10): e1011698. https://doi.org/10.1371/journal.ppat.1011698

Editor: Mary Ann Jabra-Rizk, University of Maryland, Baltimore, UNITED STATES

Published: October 19, 2023

Copyright: © 2023 Carty et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The work was supported by National Institutes of Allery and Infectious Disease (R01AI177604 to S.T). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Candida auris, is an emerging multidrug-resistant human fungal pathogen that predominately colonizes the skin. C. auris has been classified as an urgent threat by the US Centers for Disease Control and Prevention (CDC) Antibiotic Threats Report (2019) and ranked in the critical priority group by the World Health Organization (WHO) in a recently released list of fungal priority pathogens [1,2]. C. auris is found in acute care settings and long-term care facilities and where it can spread leading to systemic infections [3–6]. In some regions such as in India and parts of South Africa, C. auris has now surpassed Candida albicans as the most common Candida bloodstream species with the mortality rate ranging from 40% to 60% among infected patients [7,8]. Risk factors for C. auris colonization and infection include extensive exposure to healthcare; advanced age; chronic medical conditions including diabetes mellitus, chronic renal disease, and immune compromise; and exposure to broad-spectrum antibiotics [4,9]. Several isolates of C. auris have been identified that exhibit resistance to the azoles, polyenes, and echinocandins, the 3 major classes of FDA-approved antifungal drugs. The ability of C. auris to spread quickly in medical setting in coordination with this potential drug resistance poses significant challenges when attempting to treat infections [8,10,11]. C. auris isolates were mainly classified under 4 clades based on whole genome sequencing data of clinical strains [8]. Differences in distribution, virulence, and phenotypic properties between different clades were recently studied (Table 1).

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Table 1. Differences between 4 clades of C. auris.

https://doi.org/10.1371/journal.ppat.1011698.t001

How does C. auris spread in healthcare settings?

Unlike many other Candida species, C. auris efficiently colonizes the skin leading to contamination of the patient’s environment [21]. This phenotype likely plays a role in C. auris’ ability to cause healthcare-associated outbreaks. C. auris can colonize nares, palms, fingertips, axilla, inguinal crease, and toe webs [3,22], and colonization can lead to contamination of surfaces including floors, bed rails, bed sheet, bed hand controllers, bed side trolley, mobile phones, chairs, bed trays, air conditioning wings, and sinks. C. auris can persist for up to 2 weeks on dry surfaces and it has been detected on surfaces with little to no patient contact and infrequent healthcare worker contact such as closet cabinets, door handles, and alcohol gel dispensers [21]. Medical equipment that comes in contact with patients has also been linked to transmission as C. auris has been detected on temperature probes, blood pressure cuffs, glucometers, intravenous poles, oxygen masks, housekeeping carts, dialysis equipment, ultrasound machines, computer monitors, and keypads [22,23]. While these findings suggest the contaminated inanimate environment plays a role in cross-transmission of C. auris in healthcare settings, the relative contribution of direct transmission via fomites, patient-to-patient, or environment-to-patient transmission via healthcare provider have not yet been defined. Further studies are essential to understand what contributes to C. auris’s persistence in the environment and how this leads to infection.

How do we identify C. auris isolates on the patient and in the environment?

C. auris infections can present similarly to other fungal infections, and drug-resistant fungal strains can phenotypically behave like antibiotic susceptible isolates when not challenged with drug. As such, it is critical the medical community have the ability to detect C. auris on the skin and quickly determine a particular culture’s antifungal susceptibility. A variety of PCR-based assays have been established to identify C. auris in the healthcare environment and in waste water [24,25] and real-time PCR and loop-mediated isothermal amplification-based assays have been developed to screen for C. auris on patient’s skin [26,27]. In addition, standard PCR-based assays that do not require advanced infrastructure can probe for C. auris-specific GPI protein encoding genes [28]. As PCRs take a couple of hours to run and process, these tests provide relatively quick surveillance of an environment or patient. In addition, T2 Magnetic Resonance system-based assays originally designed as rapid diagnostic platform to detect pathogens in blood samples have also been developed to detect C. auris 5 CFU/ml from the skin [29].

The combination of efficient environmental and patient surveillance testing is critical to the control and effective treatment of C. auris in medical facilities. One, current limitation of these assays is that drug resistance, for the most part, cannot be determined using these techniques. C. auris has been shown to use a variety of mechanisms including changes in ploidy and transcription to quickly alter drug susceptibility [30,31]. As such, traditional growth assays must be used to determine antifungal susceptibility. As we learn more about C. auris drug resistance mechanisms, developing quick molecular tests such as assays to detect FKS1 mutations to determine susceptibility to echinocandins can help in the future [32].

How can we genetically manipulate C. auris?

C. auris, along with human pathogens C. albicans, C. tropicalis, and C. parapsilosis are members of the CTG fungal clade where the CTG codon is primarily translated as serine as opposed to leucine [33]. C. auris displays high salt tolerance that potentially plays a role in its ability to colonize the high salt environment of the skin. In addition, isolates of C. auris have been shown to be naturally resistant to many antifungal compounds distinguishing it from other CTG species [34]. Analysis of the C. auris genome sequence suggests that copy number variation and mutation of transporters, lipases, and drug targets could play roles in these phenotypes [20]. The efficient and accurate manipulation of the C. auris genome is critical to understanding the underlying mechanisms that support such phenotypes. Since the C. auris was genome sequenced, a number of methodologies have been developed to determine the origins of these phenotypes [35]. Forward genetic screens using Agrobacterium-mediated transformation (AtMT) have successfully been employed on C. auris [36]. In AtMT, a nourseothricin (NATr) selectable marker is incorporated into the Agrobacterium tumefaciens Ti plasmid. This is then transformed into A. tumefaciens strain EHA105 that contains the virulence genes required for recruitment of the T-DNA. Co-culturing the modified A. tumefaciens and C. auris results in gene disruption by the plasmid while conferring nourseothricin resistance. C. auris transformants are selected based on resultant phenotypes, and whole genome sequencing is completed to identify disrupted genes. This approach has been used to screen for genes important for cellular morphology. Mutants responsible for changes in morphology were recovered in all 4 clades at rates comparable to experiments performed in other yeast species [37]. Once genes of interest are identified, reverse genetics approaches can be applied to confirm the role of identified genes in the observed phenotype.

Investigators have a number of choices when applying reverse genetics to interrogate C. auris. As has been done with a variety of other fungi, direct homologous recombination methods have been employed with success to disrupt genes of interest [38]. In addition, CRISPR-Cas9 systems have also been applied to C. auris. These systems must be incorporated into the C. auris genome, as to date C. auris has not been shown to be able to maintain plasmids. The permanent incorporation of CRISPR components and selective markers to the genome presents a challenge as these components can limit the ability to further genetically manipulate a strain. Investigators have sought to mitigate this challenge in a variety of ways. Direct transformation of CRISPR Cas9 RNA protein complexes into C. auris using electroporation can be used to edit the C. auris genome [39]. Furthermore, recyclable CRISPR-mediated systems that leverage lithium acetate transformation protocols have been optimized for C. auris. Cas9/sgRNA cassettes marked with either Natr or hygromycinr also containing regions of homology to the LEU2 locus facilitate insertion of CRISPR components to the genome while simultaneously disrupting LEU2 [40]. Cells that have incorporated the CRISPR machinery will grow on drug but require leucine. Once CRISPR-mediated genome editing has been completed, transformants are plated on synthetic complete media lacking leucine to select for the reconstitution of LEU2 by homologous recombination and resultant recycling of Cas9-sgRNA insertions from the genome, thus enabling investigators to serially edit the C. auris genome.

What model organisms can we use to study C. auris pathogenesis?

Animal models that accurately recapitulate C. auris infection are critical to understanding pathogenesis. Although there are differences in skin biology between humans and mice [41], mouse models offer numerous advantages when studying virulence. Genetically modified animals and well-characterized immunological tools are available and are widely used to understand skin infection pathogenesis in vivo [18]. For example, a recent study by Huang and colleagues utilized knock out mouse models to dissect the contribution of IL-17-mediated innate and adaptive immune response in C. auris skin colonization [18]. Furthermore, recent studies compared the virulence potential of C. auris and other Candida species including C. albicans using immunocompetent and immunocompromised mice models of systemic infection [13,42,43]. C. auris elicits less immunoinflammatory response than C. albicans, and this differential response correlates with distinctions in cell wall structure [43]. C. albicans is a commensal yeast and it is likely its surface determinants have coevolved with the human immune system. C. auris is not an obligate commensal, but can colonize different host niches including skin, gut, and internal organs [18,43,44]. Comparing differences between the immune response to these pathogens have the potential to provide insights into how virulence mechanisms between these pathogens differ.

Aside from mouse, other model systems such as Zebrafish [45], Galleria mellonella [46], Caenorhabditis elegans [47], and Drosophila melanogaster [48] are utilized to study C. auris colonization and pathogenesis and can provide distinct advantages to mammalian models. Furthermore, ex vivo models such as human and pig skin can be used to conduct C. auris colonization and biofilm studies [41,49–51]. Collectively, depending on the type of experiment, invertebrate whole animal, mouse, and ex vivo skin models can be utilized to investigate fungal virulence and host–pathogen interactions.

What are the current decolonization and disinfection strategies used to control C. auris?

Decolonization in patients and environmental decontamination of C. auris is critical to prevent and control the spread of C. auris infections. Currently, there is no effective skin decolonization strategy for C. auris. Chlorhexidine gluconate (CHG) skin wash is used in some facilities to reduce the skin burden of multidrug-resistant microorganisms including C. auris. However, only high concentrations of CHG (≥625 μg/ml), which are rarely achieved on the skin, were shown to be effective for reducing the burden of C. auris on the skin in 1 study [3]. Persistent colonization has been reported in spite of using this antiseptic [3,52,53]. Further, using effective disinfectants is critical for the prevention and control of C. auris in the environment. The most current CDC recommendations for infection control can be found on the CDC website and include a list of recommended environmental disinfectants and other recommended practices [54]. These recommendations for disinfectants were based on recent studies showing efficacy of hydrogen peroxide or alcohol-based active compounds against C. auris and ineffectiveness of products based on quaternary ammonium chemistry (QAC) [55,56]. In addition, recently C. auris was also detected in the wastewater samples in Nevada, United States of America [25]. Further studies are needed to develop novel strategies to evaluate the efficacy of currently available disinfectants and control measures in real-world settings.

References

  1. 1. Kadri SS. Key Takeaways From the U.S. CDC’s 2019 Antibiotic Resistance Threats Report for Frontline Providers. Crit Care Med. 2020;48(7):939–45. pmid:32282351; PubMed Central PMCID: PMC7176261.
  2. 2. WHO fungal priority pathogens list to guide research, development and public health action. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 30 IGO. Available from: https://www.who.int/publications/i/item/9789240060241. WHO, 2022.
    • 3. Proctor DM, Dangana T, Sexton DJ, Fukuda C, Yelin RD, Stanley M, et al. Integrated genomic, epidemiologic investigation of Candida auris skin colonization in a skilled nursing facility. Nat Med. 2021;27(8):1401–9. Epub 20210621. pmid:34155414.
    • 4. Rossow J, Ostrowsky B, Adams E, Greenko J, McDonald R, Vallabhaneni S, et al. Factors Associated With Candida auris Colonization and Transmission in Skilled Nursing Facilities With Ventilator Units, New York, 2016–2018. Clin Infect Dis. 2021;72(11):e753–e760. pmid:32984882; PubMed Central PMCID: PMC8155826.
    • 5. Mathur P, Hasan F, Singh PK, Malhotra R, Walia K, Chowdhary A. Five-year profile of candidaemia at an Indian trauma centre: High rates of Candida auris blood stream infections. Mycoses. 2018;61(9):674–80. Epub 20180705. pmid:29738604.
    • 6. Horton MV, Johnson CJ, Kernien JF, Patel TD, Lam BC, Cheong JZA, et al. Candida auris Forms High-Burden Biofilms in Skin Niche Conditions and on Porcine Skin. mSphere. 2020;5(1). Epub 20200122. pmid:31969479; PubMed Central PMCID: PMC6977180.
    • 7. Ruiz-Gaitan A, Moret AM, Tasias-Pitarch M, Aleixandre-Lopez AI, Martinez-Morel H, Calabuig E, et al. An outbreak due to Candida auris with prolonged colonisation and candidaemia in a tertiary care European hospital. Mycoses. 2018;61(7):498–505. Epub 20180608. pmid:29655180.
    • 8. Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, et al. Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses. Clin Infect Dis. 2017;64(2):134–40. Epub 20161020. pmid:27988485; PubMed Central PMCID: PMC5215215.
    • 9. Vallabhaneni S, Jackson BR, Chiller TM. Candida auris: An Emerging Antimicrobial Resistance Threat. Ann Intern Med. 2019;171(6):432–3. Epub 20190730. pmid:31357215.
    • 10. Du H, Bing J, Hu T, Ennis CL, Nobile CJ, Huang G. Candida auris: Epidemiology, biology, antifungal resistance, and virulence. PLoS Pathog. 2020;16(10):e1008921. Epub 20201022. pmid:33091071; PubMed Central PMCID: PMC7581363.
    • 11. Chowdhary A, Prakash A, Sharma C, Kordalewska M, Kumar A, Sarma S, et al. A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance. J Antimicrob Chemother. 2018;73(4):891–899. pmid:29325167.
    • 12. Chow NA, Munoz JF, Gade L, Berkow EL, Li X, Welsh RM, et al. Tracing the Evolutionary History and Global Expansion of Candida auris Using Population Genomic Analyses. mBio. 2020;11(2). Epub 20200428. pmid:32345637; PubMed Central PMCID: PMC7188998.
    • 13. Forgacs L, Borman AM, Prepost E, Toth Z, Kardos G, Kovacs R, et al. Comparison of in vivo pathogenicity of four Candida auris clades in a neutropenic bloodstream infection murine model. Emerg Microbes Infect. 2020;9(1):1160–1169. pmid:32486923; PubMed Central PMCID: PMC7448943.
    • 14. Fan S, Yue H, Zheng Q, Bing J, Tian S, Chen J, et al. Filamentous growth is a general feature of Candida auris clinical isolates. Med Mycol. 2021;59(7):734–40. Epub 2021/01/24. pmid:33485272; PubMed Central PMCID: PMC8257410.
    • 15. Malavia-Jones D, Farrer RA, Stappers MHT, Edmondson MB, Borman AM, Johnson EM, et al. Strain and temperature dependent aggregation of Candida auris is attenuated by inhibition of surface amyloid proteins. Cell Surf. 2023;10:100110. Epub 20230724. pmid:37559873; PubMed Central PMCID: PMC10407437.
    • 16. Welsh RM, Sexton DJ, Forsberg K, Vallabhaneni S, Litvintseva A. Insights into the Unique Nature of the East Asian Clade of the Emerging Pathogenic Yeast Candida auris. J Clin Microbiol. 2019;57(4). Epub 2019/02/15. pmid:30760535; PubMed Central PMCID: PMC6440783.
    • 17. Ahmad S, Asadzadeh M. Strategies to Prevent Transmission of Candida auris in Healthcare Settings. Curr Fungal Infect Rep. 2023;17(1):36–48. Epub 2023/02/01. pmid:36718372; PubMed Central PMCID: PMC9878498.
    • 18. Huang X, Hurabielle C, Drummond RA, Bouladoux N, Desai JV, Sim CK, et al. Murine model of colonization with fungal pathogen Candida auris to explore skin tropism, host risk factors and therapeutic strategies. Cell Host Microbe. 2021;29(2):210–21 e6. Epub 20201231. pmid:33385336; PubMed Central PMCID: PMC7878403.
    • 19. Brandt P, Mirhakkak MH, Wagner L, Driesch D, Moslinger A, Fander P, et al. High-Throughput Profiling of Candida auris Isolates Reveals Clade-Specific Metabolic Differences. Microbiol Spectr. 2023;11(3):e0049823. Epub 2023/04/25. pmid:37097196; PubMed Central PMCID: PMC10269459.
    • 20. Munoz JF, Gade L, Chow NA, Loparev VN, Juieng P, Berkow EL, et al. Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species. Nat Commun. 2018;9(1):5346. Epub 20181217. pmid:30559369; PubMed Central PMCID: PMC6297351.
    • 21. Sexton DJ, Bentz ML, Welsh RM, Derado G, Furin W, Rose LJ, et al. Positive Correlation Between Candida auris Skin-Colonization Burden and Environmental Contamination at a Ventilator-Capable Skilled Nursing Facility in Chicago. Clin Infect Dis. 2021;73(7):1142–1148. pmid:33978150; PubMed Central PMCID: PMC8492228.
    • 22. Yadav A, Singh A, Wang Y, Haren MHV, Singh A, de Groot T, et al. Colonisation and Transmission Dynamics of Candida auris among Chronic Respiratory Diseases Patients Hospitalised in a Chest Hospital, Delhi, India: A Comparative Analysis of Whole Genome Sequencing and Microsatellite Typing. J Fungi (Basel). 2021;7(2). Epub 20210126. pmid:33530297; PubMed Central PMCID: PMC7910912.
    • 23. Eyre DW, Sheppard AE, Madder H, Moir I, Moroney R, Quan TP, et al. A Candida auris Outbreak and Its Control in an Intensive Care Setting. N Engl J Med. 2018;379(14):1322–1331. pmid:30281988.
    • 24. Freitas BL, Leach L, Chaturvedi V, Chaturvedi S. Reverse Transcription-Quantitative Real-Time PCR (RT-qPCR) Assay for the Rapid Enumeration of Live Candida auris Cells from the Health Care Environment. J Clin Microbiol. 2022;60(2):e0077921. Epub 2021/12/09. pmid:34878804; PubMed Central PMCID: PMC8849214.
    • 25. Barber C, Crank K, Papp K, Innes GK, Schmitz BW, Chavez J, et al. Community-Scale Wastewater Surveillance of Candida auris during an Ongoing Outbreak in Southern Nevada. Environ Sci Technol. 2023;57(4):1755–63. Epub 20230119. pmid:36656763; PubMed Central PMCID: PMC9893721.
    • 26. Sexton DJ, Kordalewska M, Bentz ML, Welsh RM, Perlin DS, Litvintseva AP. Direct Detection of Emergent Fungal Pathogen Candida auris in Clinical Skin Swabs by SYBR Green-Based Quantitative PCR Assay. J Clin Microbiol. 2018;56(12). Epub 2018/09/21. pmid:30232130; PubMed Central PMCID: PMC6258843.
    • 27. Yamamoto M, Alshahni MM, Tamura T, Satoh K, Iguchi S, Kikuchi K, et al. Rapid Detection of Candida auris Based on Loop-Mediated Isothermal Amplification (LAMP). J Clin Microbiol. 2018;56(9). Epub 2018/06/29. pmid:29950329; PubMed Central PMCID: PMC6113467.
    • 28. Alvarado M, Bartolome Alvarez J, Lockhart SR, Valentin E, Ruiz-Gaitan AC, Eraso E, et al. Identification of Candida auris and related species by multiplex PCR based on unique GPI protein-encoding genes. Mycoses. 2021;64(2):194–202. Epub 2020/11/01. pmid:33128788.
    • 29. Sexton DJ, Bentz ML, Welsh RM, Litvintseva AP. Evaluation of a new T2 Magnetic Resonance assay for rapid detection of emergent fungal pathogen Candida auris on clinical skin swab samples. Mycoses. 2018;61(10):786–90. Epub 2018/06/26. pmid:29938838.
    • 30. Bing J, Hu T, Zheng Q, Muñoz JF, Cuomo CA, Huang G. Experimental Evolution Identifies Adaptive Aneuploidy as a Mechanism of Fluconazole Resistance in Candida auris. Antimicrob Agents Chemother. 2020;65(1). Epub 2020/10/21. pmid:33077664; PubMed Central PMCID: PMC7927865.
    • 31. Carolus H, Pierson S, Munoz JF, Subotic A, Cruz RB, Cuomo CA, et al. Genome-Wide Analysis of Experimentally Evolved Candida auris Reveals Multiple Novel Mechanisms of Multidrug Resistance. mBio. 2021;12(2). Epub 2021/04/07. pmid:33820824; PubMed Central PMCID: PMC8092288.
    • 32. Sharma D, Paul RA, Rudramurthy SM, Kashyap N, Bhattacharya S, Soman R, et al. Impact of FKS1 Genotype on Echinocandin In Vitro Susceptibility in Candida auris and In Vivo Response in a Murine Model of Infection. Antimicrob Agents Chemother. 2022;66(1):e0165221. Epub 20211115. pmid:34780273; PubMed Central PMCID: PMC8765266.
    • 33. Santos MA, Gomes AC, Santos MC, Carreto LC, Moura GR. The genetic code of the fungal CTG clade. C R Biol. 2011;334(8–9):607–11. Epub 2011/08/09. pmid:21819941.
    • 34. Allert S, Schulz D, Kammer P, Grossmann P, Wolf T, Schauble S, et al. From environmental adaptation to host survival: Attributes that mediate pathogenicity of Candida auris. Virulence. 2022;13(1):191–214. Epub 2022/02/11. pmid:35142597; PubMed Central PMCID: PMC8837256.
    • 35. Chatterjee S, Alampalli SV, Nageshan RK, Chettiar ST, Joshi S, Tatu US. Draft genome of a commonly misdiagnosed multidrug resistant pathogen Candida auris. BMC Genomics. 2015;16(1):686. Epub 2015/09/09. pmid:26346253; PubMed Central PMCID: PMC4562351.
    • 36. Santana DJ, O’Meara TR. Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains. Nat Commun. 2021;12(1):7197. Epub 2021/12/12. pmid:34893621; PubMed Central PMCID: PMC8664941.
    • 37. Bundock P, den Dulk-Ras A, Beijersbergen A, Hooykaas PJ. Trans-kingdom T-DNA transfer from Agrobacterium tumefaciens to Saccharomyces cerevisiae. EMBO J. 1995;14(13):3206–14. Epub 1995/07/03. pmid:7621833; PubMed Central PMCID: PMC394382.
    • 38. Bravo Ruiz G, Lorenz A. Genetic Transformation of Candida auris via Homology-Directed Repair Using a Standard Lithium Acetate Protocol. Methods Mol Biol. 2022;2517:95–110. Epub 2022/06/09. pmid:35674948.
    • 39. Grahl N, Demers EG, Crocker AW, Hogan DA. Use of RNA-Protein Complexes for Genome Editing in Non-albicans Candida Species. mSphere. 2017;2(3). Epub 2017/06/29. pmid:28657070; PubMed Central PMCID: PMC5480035.
    • 40. Ennis CL, Hernday AD, Nobile CJ. A Markerless CRISPR-Mediated System for Genome Editing in Candida auris Reveals a Conserved Role for Cas5 in the Caspofungin Response. Microbiol Spectr. 2021;9(3):e0182021. Epub 20211103. pmid:34730409; PubMed Central PMCID: PMC8567271.
    • 41. Eix EF, Nett JE. Modeling Candida auris skin colonization: Mice, swine, and humans. PLoS Pathog. 2022;18(9):e1010730. Epub 20220908. pmid:36074786; PubMed Central PMCID: PMC9455849.
    • 42. Xin H, Mohiuddin F, Tran J, Adams A, Eberle K. Experimental Mouse Models of Disseminated Candida auris Infection. mSphere. 2019;4(5). Epub 20190904. pmid:31484737; PubMed Central PMCID: PMC6731527.
    • 43. Wang Y, Zou Y, Chen X, Li H, Yin Z, Zhang B, et al. Innate immune responses against the fungal pathogen Candida auris. Nat Commun. 2022;13(1):3553. Epub 2022/06/22. pmid:35729111; PubMed Central PMCID: PMC9213489.
    • 44. Abe M, Katano H, Nagi M, Higashi Y, Sato Y, Kikuchi K, et al. Potency of gastrointestinal colonization and virulence of Candida auris in a murine endogenous candidiasis. PLoS ONE. 2020;15(12):e0243223. Epub 20201202. pmid:33264362; PubMed Central PMCID: PMC7710084.
    • 45. Horton MV, Johnson CJ, Zarnowski R, Andes BD, Schoen TJ, Kernien JF, et al. Candida auris Cell Wall Mannosylation Contributes to Neutrophil Evasion through Pathways Divergent from Candida albicans and Candida glabrata. mSphere. 2021;6(3):e0040621. Epub 20210623. pmid:34160238; PubMed Central PMCID: PMC8265655.
    • 46. Smith DFQ, Dragotakes Q, Kulkarni M, Hardwick JM, Casadevall A. Galleria mellonella immune melanization is fungicidal during infection. Commun Biol. 2022;5(1):1364. Epub 20221212. pmid:36510005; PubMed Central PMCID: PMC9744840.
    • 47. Hernando-Ortiz A, Mateo E, Perez-Rodriguez A, de Groot PWJ, Quindos G, Eraso E. Virulence of Candida auris from different clinical origins in Caenorhabditis elegans and Galleria mellonella host models. Virulence. 2021;12(1):1063–1075. pmid:33843456; PubMed Central PMCID: PMC8043173.
    • 48. Wurster S, Albert ND, Kontoyiannis DP. Drosophila melanogaster as a Rapid and Reliable In Vivo Infection Model to Study the Emerging Yeast Pathogen Candida auris. Methods Mol Biol. 2022;2517:299–316. pmid:35674964.
    • 49. Nakatsuji T, Chen TH, Narala S, Chun KA, Two AM, Yun T, et al. Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis. Sci Transl Med. 2017;9(378). pmid:28228596; PubMed Central PMCID: PMC5600545.
    • 50. Corzo-Leon DE, Mark C, MacCallum DM, Munro CA. A Human Ex Vivo Skin Model to Study Candida auris Biofilms. Methods Mol Biol. 2022;2517:259–267. pmid:35674961.
    • 51. Eix EF, Johnson CJ, Wartman KM, Kernien JF, Meudt JJ, Shanmuganayagam D, et al. Ex Vivo Human and Porcine Skin Effectively Model Candida auris Colonization, Differentiating Robust and Poor Fungal Colonizers. J Infect Dis. 2022;225(10):1791–1795. pmid:35267041; PubMed Central PMCID: PMC9113498.
    • 52. Ku TSN, Walraven CJ, Lee SA. Disinfectants and Implications for Infection Control. Front Microbiol. 2018;9:726. Epub 20180412. pmid:29706945; PubMed Central PMCID: PMC5906573.
    • 53. Biswal M, Rudramurthy SM, Jain N, Shamanth AS, Sharma D, Jain K, et al. Controlling a possible outbreak of Candida auris infection: lessons learnt from multiple interventions. J Hosp Infect. 2017;97(4):363–70. Epub 20170919. pmid:28939316.
    • 54. Infection Prevention and Control for Candida auris. Available from: https://www.cdc.gov/fungal/candida-auris/c-auris-infection-control.html.
      • 55. Cadnum JL, Shaikh AA, Piedrahita CT, Sankar T, Jencson AL, Larkin EL, et al. Effectiveness of Disinfectants Against Candida auris and Other Candida Species. Infect Control Hosp Epidemiol. 2017;38(10):1240–3. Epub 20170810. pmid:28793937.
      • 56. Sexton DJ, Welsh RM, Bentz ML, Forsberg K, Jackson B, Berkow EL, et al. Evaluation of nine surface disinfectants against Candida auris using a quantitative disk carrier method: EPA SOP-MB-35. Infect Control Hosp Epidemiol. 2020;41(10):1219–21. Epub 20200630. pmid:32600492.