Candida auris
1. Classification
Higher order taxa
Domain: Eukaryota; Kingdom: Fungi; Phylum: Ascomycota; Class: Saccharomycetes; Order: Saccharomycetales; Family: Metschnikowia Ceae; Genus: Candida; Species: Candida auris
2. Description and significance
Discovered in 2009, Candida Auris is a fungus that infiltrates the bloodstream and afflicts the central nervous system of the human body. Candida Auris particularly affects immunocompromised patients (Cortegani 2018). C. auris can be easily transmitted on a variety of surfaces including unsterilized medical equipment when used for multiple patients (Welsh 2018), as well as via one’s skin, rectum, akilla and stool (Cortegani 2019). C. auris infections are of clinical significance because it exhibits multilayer drug resistance leading to a high mortality rate (Cortegani 2018). Identification of C. auris infections is often difficult, as it is commonly misidentified as other Candida species. Multiple strains of this fungus exist, each developing independently on three different continents (Casadevall 2019). Due to its high levels of transmissibility, multidrug resistance, and mortality rates, C. auris is particularly dangerous to immunocompromised patients and is a growing area of research within the healthcare system.
3. Genome structure
Candida auris’s genome has a total of 5,714 genes, 45.11% G:C base pairs (Sharma 2015). The genome contains genes for the ABC transporter family (Chatterjee 2016). Whole genome sequencing identified four different clades of C. auris, distinguished by region; East Asia, South Asia, Africa and South America (Rossato 2018). In addition, based on analysis of single nucleotide polymorphisms, C. auris displays low genetic diversity between strains within each clade. This finding suggests high levels of clonality within specific clades (Lockhart 2017). The emergence of the four different populations from the three continents is thought to be independent and almost simultaneous (Rossato 2018).
4. Cell structure
The cells of C. auris are oval shaped; however, it has been hypothesized that this oval shape changes depending on environmental conditions (Larkin 2017). C. auris colonies have been observed forming white, or cream, colonies on sabouraud dextrose agar and pink colonies on CHROM agar (Spivak 2018). Unlike many other Candida species, C. auris does not form chlamydospores (Larkin 2017). C. auris is considered Gram-negative (Sekyere 2018). In addition to the presence of a thin layer of peptidoglycan, chitin is also present in high concentrations within the cell wall of C. auris (Sekyere 2018). Also abundant in the cell wall of C. auris is mannan, a highly branched polysaccharide (Eurofins 2019). More specifically, O-linked mannans constitute 15% of the cell wall’s total mannan content (Navarro-Arias 2019).
5. Metabolic processes
C. auris produces metabolites that inhibit the growth of its own hyphae (Semreen 2019). C. auris grows optimally at 37 degrees Celsius, but has the ability to survive up to 42 degrees Celsius (Borman 2016).
C. auris can grow efficiently with many different carbon sources including glucose, sucrose, maltose, D- trehalose, D- raffinose, and D- melezitose (Sekyere 2018). Nitrogen sources include ammonium sulfate, cadaverine, and L- lysine (Sekyere 2018). Compared to other closely related species, such as C. albicans, C. auris has been shown to upregulate proteins found in the TCA cycle. Consequently, C. auris favors respiration, increasing ATP production as opposed to less efficient anaerobic processes (Zamith-Miranda 2019). Upregulation of critical TCA cycle proteins and a reliance on organic molecules for efficient growth likely classifies C. auris as a chemoorganoheterotroph. Concerning stress response, it was recently discovered that C. auris has a unique stress resistance profile mediated by the Hog1 stress-activated protein kinase (Day 2018). The unique stress responses activated by Hog1 stress-activated protein kinase promotes the virulence of C. auris and may provide an effective target for antifungal therapeutics (Day 2018).
6. Ecology
C. Auris is not detected outside a host in the natural environment. However, the fungus is able to survive on surfaces for a few weeks (Jackson 2019). Related species have been discovered in plants, insects, and aquatic environments (Jackson 2019). The fungus is also able to tolerate salt, which may lead to aggregation, leading to difficult treatment (Sherry 2017). C. auris can also be tolerant to higher temperature than other Candida species. The combined thermophilic and halophilic tolerances in theory may allow C. Auris to live in ponds or tidal pools (Jackson 2019).
C. Auris is found in four world regions: East Asia, South Asia, Africa, and South America (Jackson 2019). C. auris is commonly found co-colonizing with Gram-negative carbapenemase producing bacteria in clinical settings (CDC).
7. Pathology
C. Auris is commonly found in the bloodstream and once it has infiltrated the bloodstream, the fungi may easily be transferred through the body (Casadevall 2019). Candida auris infections lead to death every 1 in 3 patients (CDC). Although samples of C. Auris have been retrieved in patient’s urine and respiratory tract, it does not necessarily infect these areas in an active manner (CDC). Patients with comorbidities have an increased infection and mortality rate (CDC). Specifically in humans, C. Auris colonizes a patient’s skin, nose, ears, mouth, rectum or vagina (Jackson 2019).
Identification can prove challenging with Candida auris. Appearance can be used to aid identification, but Candida auris is indistinguishable from other Candida species under a microscope (CDC). The CDC recommends that real-time PCR be used to identify Candida auris (CDC). For institutions lacking appropriate resources to produce a real-time PCR test, the agar media CHROMagar is the only conventional agar plate that allows for differentiation from common Candida species (CDC). MALDI-TOF mass spectrometry is the most accurate identification method, however, some databases do not allow for Candida auris identification. Additionally, MALDI-TOF is not a readily viable option in most clinical settings (CDC).
C. auris infection outbreaks can prove challenging to control. Molecular methods of detection, such as MALDI-TOF, are required for official diagnosis of an infection of C. auris (CDC). C. auris infections can last for months and withstand common disinfectants and antifungal treatments (Sherry 2017). Consequently, preventing C. auris infection is of critical importance. In the case of infection, treatment with echinocandins, to which C. auris isolates have been shown to be susceptible to, is the suggested initial treatment, though no optimal treatment plan has been identified (Spivak 2018).
8. Current Research
Current research on C. auris is focused on further characterization of the molecular mechanisms that allow for multidrug resistance, as well as improved detection methods to distinguish it from other Candida species. Currently, the standard method for C. auris testing is RT-PCR which, while effective, is both time consuming and costly (Leach 2018). Recent developments, such as the production of single tube PCR methods, allow for fast, inexpensive detection that is more accessible and highly specific (Theill 2018).
Numerous studies have been conducted with the goal of elucidating the mechanisms of multidrug resistance and potential treatments or preventions. Other studies have investigated whether existing therapies or known antifungal molecules that are not typically used for Candida infections may be effective in combating C. auris. One such instance of this is the antidepressant drug Sertraline. Treatment of C. auris with Sertraline in vitro was able to effectively inhibit growth and disrupt biofilm production (Gowri 2020). Similar growth inhibition and subsequent cell death was seen after treatment of C. auris with salivary histatin 5, a salivary peptide that provides one of the first lines of defense in the human innate immune system (Pathirana 2018). Such results provide the potential to develop more effective antifungal treatments and shed light on the mechanisms that make up the foundation of C. auris drug resistance.
Although treatment of C. auris infections is critical, preventing the spread of this fungus in clinical settings is of equal importance. C. auris has been shown to spread easily on non-sterile surfaces; however, vaccination may reduce the risk of transmission. NDV-3A, a vaccine based on a cell surface protein of C. auris, was shown to reduce infection in mice models (Singh 2019). This vaccine was able to disrupt the biofilm produced by the fungus and aid in bolstering an immune response against infection (Singh 2019). In the absence of a vaccine, more efficient sterilization methods are being developed to reduce surface transmission of C. auris. A recent study shows that, under certain parameters, UV-C could be used to kill C. auris (De Groot 2019). Methods such as these may aid to limit the infections caused by C. auris.
9. References
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2. Casadevall, A., Kontoyiannis, D. P., & Robert, V. 2019. On the emergence of Candida auris: climate change, azoles, swamps, and birds. MBio, 10, e01397-19.
3. 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(1):686
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5. Cortegiani, A., G. Misseri, A. Giarratano, M. Bassetti, and D. Eyre. 2019. The global challenge of Candida auris in the intensive care unit. Crit. Care 23:150.
6. Day, A.M., M. M. McNiff, A. da Silva Dantas, N.A.R. Gow, and J. Quinn. 2018. Hog1 Regulates Stress Tolerance and Virulence in the Emerging Fungal Pathogen Candida auris. mSphere, 3(5):506-18.
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8. Eurofins, 2019. Food & Feed Testing. Yeast Cell Wall Polysaccharides: 𝛃- Glucans & Mannans.
9. Gowri M, Jayashree B, Jeyakanthan J, and Girija EK. 2020. Sertraline as a promising antifungal agent: inhibition of growth and biofilm of Candida auris with special focus on the mechanism of action in vitro. J Appl Microbiol, 128(2):426-437
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13. Lockhart, S.R., Etienne, K.A., Vallabhaneni, S., Farooqi, J., Chowdhary, A., Govender, N.P., Colombo, A.L., Calvo, B., Cuomo, C.A., Desjardins, C.A., Berkow, E.L. 2017. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses. Clinical Infectious Diseases, 64(2), 134-140.
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20. Sherry, L., G. Ramage, R. Kean, A. Borman, E. M. Johnson, M. D. Richardson, R. Rautemaa-Richardson. 2017. Biofilm-forming capability of highly-virulent, multidrug-resistant Candida auris. Emerging Infectious Diseases, 2:328-331,
21. Sharma C, Kumar N, Meis JF, Pandey R, Chowdhary A. 2015 Draft Genome Sequence of a Fluconazole-Resistant Candida auris Strain from a Candidemia Patient in India. Genome Announc.3(4)
22. Singh S, Uppuluri P, Mamouei Z, Alqarihi A, Elhassan H, French S, Lockhart SR, Chiller T, Edwards JE Jr, and Ibrahim AS. 2019. The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection. PLoS Pathog, 15(8):1007460.
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24. Theill, L., C. Dudiuk, S. Morales-Lopez, I. Berrio, J. Y. Rodríguez, A. Marin , S. Gamarra, and G. Garcia-Effron. 2018. Single-tube classical PCR for Candida auris and Candida haemulonii identification. Rev Iberoam Micol, 35(2):110-112.
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Edited by William D. Denton, Sam Van Roy, Vanessa L. Stahl, Anna Bogursky, Kate M. Workman, students of Jennifer Bhatnagar for BI 311 General Microbiology, 2020, Boston University.
Author contributions: A.B. wrote the introduction section; A.B., K.M.W., V.L.S., wrote the section of genome structure; K.M.W., V.L.S., S.V., wrote the section on cell structure; K.M.W., V.L.S., W.D.D., wrote the section on metabolic processes; K.M.W., S.V., wrote the section on ecology; V.L.S., S.V., W.D.D., wrote the section on pathogenicity; V.L.S., W.D.D., wrote the section on research; All authors contributed to literature research and editing of all draft versions.
