Pathogens and Disease, 78, 2020, ftaa034

doi: 10.1093/femspd/ftaa034
Advance Access Publication Date: 9 July 2020
Priority Paper

PRIORITY PAPER

Candida auris: a fungus with identity crisis

Taissa Vila1,† , Ahmed S. Sultan1,† , Daniel Montelongo-Jauregui1,† and Mary
Ann Jabra-Rizk1,2, *
1
Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD
21201, USA and 2 Department of Microbiology and Immunology, School of Medicine, University of Maryland,
Baltimore, MD 21201, USA
∗
Corresponding author: University of Maryland-Baltimore, School of Dentistry, 650 W. Baltimore Street, 7 North #7253, Baltimore, MD 21201, USA. Tel:
410-706-0508; Fax: 410-706-0519; E-mail: [email protected]
One sentence summary: Candida auris is a new multi-drug resistant fungal species that has puzzlingly emerged as a pathogen causing persistent
outbreaks in healthcare facilities world-wide with an overall mortality rate approaching 68%.
†
These authors contributed equally to this work.
Editor: Anuradha Chowdhary

ABSTRACT
Candida auris is a new fungal species that has puzzlingly and simultaneously emerged on five continents. Since its
identification in 2009, the scientific community has witnessed an exponential emergence of infection episodes and
outbreaks in healthcare facilities world-wide. Candida auris exhibits several concerning features compared to other related
Candida species, including persistent colonization of skin and nosocomial surfaces, ability to resist common disinfectants
and to spread rapidly among patients. Resistance to multiple drug classes and misidentification by available laboratory
identification systems has complicated clinical management, and outcomes of infection have generally been poor with
mortality rates approaching 68%. Currently, the origins of C. auris are unclear, and therefore, it is impossible to determine
whether environmental and climactic changes were contributing factors in its recent emergence as a pathogen.
Nevertheless, a robust response involving rapid diagnostics, prompt interventions and implementation of precautions, are
paramount in curtailing the spread of infections by this fungal species. Importantly, there is a pressing need for the
development of new antifungal drugs. In this article, we present a brief overview highlighting some of the important
aspects of C. auris epidemiology, pathogenesis and its puzzling global emergence.

Keywords: Candida auris; fungal pathogen; drug resistance; global emergence; hospital outbreaks; high mortality

INTRODUCTION auris was first isolated in 2009 from an ear canal infection in
a patient in Japan. Although sequencing revealed that the iso-
Candida auris is a fungus that doesn’t quite behave like a fun-
late was related to other Candida species, the organism exhib-
gus. It has been dubbed a ’Superbug’, a moniker historically
ited distinct characteristics, and thus, it was considered a new
reserved for describing multi-drug resistant nosocomial bac-
species. As it was first isolated from the ear canal, it was given
teria. Candida auris has earned the title however, as this fun-
the name Candida auris (auris is Latin for ‘ear’) (Satoh et al. 2009).
gus sticks, persists and spreads like bacteria causing nosoco-
While much remains unknown about the biology of C. auris, it
mial outbreaks in healthcare facilities, and is highly resistant
has become quite evident that this new species is strikingly dif-
to antifungal drugs (Lee et al. 2011; Chakrabarti et al. 2015; Sche-
ferent from its close relatives in terms of its genetics, resilience
lenz et al. 2016; Rudramurthy et al. 2017; Eyre et al. 2018; Ruiz-
and pathogenic capabilies, to an extent that will change the
Gaitán et al. 2018; Sekyere 2018; Tsay et al. 2018; de Jong and
way we think about Candida and Candida infections (Jackson
Hagen 2019; Forsberg et al. 2019; Hamprecht et al. 2019; Lone and
et al. 2019).
Ahmad 2019; Schwartz and Dingle 2019; Wickes 2020). Candida

Received: 10 March 2020; Accepted: 7 July 2020


C The Author(s) 2020. Published by Oxford University Press on behalf of FEMS. All rights reserved. For permissions, please e-mail:

[email protected]

1
 2 Pathogens and Disease, 2020, Vol. 78, No. 4

Table 1. Major Candida auris reported outbreaks.

Countrya Date Clinical setting No. of cases Age of patient(s) Sexb Recovery site(s) Mortality Reference

Japanc 2009 Hospital 1 70 years F (1) External ear canal NAd

Satoh et al.
2009
USA (New York) 2013–17 Hospital; medical 51 21–96 years F (25) M Candidemia 27%e Adams et al.
offices (26) 2018
USA (New York) 2016–18 Healthcare facilities 277 NA NA Candidemia NA Zhu and
Leach 2019
USA (New Jersey) Total to date NA 155 NA NA NA NA CDCf
USA (Illinois) Total to date NA 288 NA NA NA NA CDC
Canada 2012–19 NA 19 NA NA NA NA Schwartz
and Dingle
2019
Spain 2016–17 Surgical ICU 41 Mean age: 58 F (15) M Candidemia 41%e Ruiz-Gaitán
years (26) et al. 2018
UK 2015–16 Cardio-thoracic 50 19–78 years F (17) M Skin/mucosa; No deaths Schelenz
center (33) candidemia (8) et al. 2016
UK 2015–17 Neurosciences ICU 70 42–64 years F (22) M Skin (axillary 17%e Eyre et al.
(48) temperature probes) 2018
Germany 2015–17 Previously 7 15–67 years F (3) M (4) Urine, candidemia No deaths Hamprecht
hospitalized abroad et al. 2019
Venezuela 2012–13 ICUs 18 2 days–72 years F (8) M (10) Candidemia 28%e Calvo et al.
2016
Colombia 2015–16 Hospitals 40 4 months–56 F (16) M Axilla and groin 43%e Armstrong et
years (24) al. 2019
Panama 2016 ICUs 9 20–78 years F (3) M (6) Urine 22%e Araúz et al.
2018
Kenya 2010–13 Hospital 45 NA NA Candidemia NA Okinda,
Kagotho and
Castanheira
2014
South Africa 2012–13 Hospitals 4 27–85 years F (0) M (4) Candidemia NA Magobo et al.
2014
South Africa 2012–16 Hospitals 451 41–68 years F (169) M Candidemia NA Govender et
(273) NA (9) al. 2018
South Africa 2016–17 Hospitals 794 34–67 years F (179) M Candidemia 45% van
(284) NA Schalkwyk,
(331) Mpembe
and
Thomas
2019
Oman 2016–17 Hospital 7 31–77 years F (3) M (4) Candidemia 57%e Al-Siyabi et
al. 2017;
Mohsin et al.
2017
Israel 2014–15 Hospital 6 42–91 years F (2) M (4) Candidemia 33% Ben- Ami,
Berman and
Novikov
2017
Kuwait 2015–17 Hospital 17 33–82 years F (6) M (9) Candidemia 53% Khan et al.
2018
Pakistan 2012–15 Hospitals 18 40–65 years F (7) M (11) Candidemia, urine 72% Lockhart et
al. 2017
India 2009–11 Hospital and 12 3 days–74 years F (7) M (5) Candidemia 33% Chowdhary,
pediatric center Sharma and
Duggal
2013
India 2011–12 ICUs 74 16–58 years F (28) M Candidemia 42%e Chakrabarti
(46) et al. 2015;
Rudra-
murthy et al.
2017
South Korea 2009 (2) 1996 (1) Hospitals 3 1–74 years F (1) M (2) Candidemia 66% Lee et al.
2011

a
Austria, Belgium, Chile, Costa Rica, Egypt, Greece, Italy, Iran, Norway, Poland, Switzerland, Taiwan, Thailand and the United Arab Emirates have reported only single
cases of C. auris; b F, female; m male; c first identified; d NA, not available; e 30 day mortality;f
CDC: https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html?CDC AA refVal=.html. Accessed 03/04, 2020.
 Vila et al. 3

Figure 1. Geographical and clade distribution of C. auris cases and outbreaks world-wide. Red circles denote reported outbreaks; concentric circles indicate more than
one outbreak, and red star (Japan) indicates location where first identified C. auris isolate was recovered in 2009.

Figure 2. Candida auris morphology and biofilm formation. (A) 3D reconstructed confocal laser scanning microscopy image of C. auris yeast cells. Cell wall chitin
stained with calcofluor white (blue); cell wall polysaccharides stained with concanavalin-A (fuchsia); white arrows: budding scars with higher polysaccharide content.
Objective magnification: 63x; cropped representative area. (B) Representative scanning electron microscopy (SEM) image of an in vivo-grown C. auris biofilm. Infected
fragments of intravascular catheters were implanted subcutaneously in dorsum of mice and biofilms were allowed to form for 72 h. SEM analysis demonstrated the
formation of a mature C. auris biofilm within the lumen of the catheter consisting of yeast cells and extracellular polysaccharide matrix (red arrow). Bar = 10 μ m.

Since its identification, the scientific community has wit- Asian (clade I), East Asian (clade II), South African (clade III) and
nessed an exponential emergence of infection episodes and South American (clade IV) (Lockhart et al. 2017, Jackson et al.
outbreaks in healthcare facilities in different regions of the 2019, Rhodes and Fisher 2019). However, wide genome sequenc-
world, and as of 31 March 31 2020, C. auris has been isolated in ing of a C. auris isolate recently recovered from a patient in Iran
41 countries (Table 1; Fig. 1) (https://www.cdc.gov/fungal/candi indicated a fifth major clade of C. auris genetically distinct from
da-auris/tracking-c-auris.html) (Chowdhary, Sharma and Dug- the four existing clades, which is now representative of a fifth
gal 2013; Magobo et al. 2014; Okinda, Kagotho and Castanheira clade (clade V) (Fig. 1) (Chow et al. 2019). Remarkably, genetic
2014; Calvo et al. 2016; Al-Siyabi et al. 2017; Mohsin et al. 2017; sequences of isolates in the different clades demonstrated that
Araúz et al. 2018; Govender et al. 2018; Khan et al. 2018; Rhodes the clades differ by tens of thousands of single-nucleotide poly-
et al. 2018; Armstrong et al. 2019; van Schalkwyk, Mpembe and morphisms (SNPs), whereas within a clade, isolates are highly
Thomas 2019). Genetic analysis of isolates revealed deep diver- related indicating that isolates within each clade are almost
gence within the C. auris species and identified four major pop- clonal (Lockhart et al. 2017). These unusual findings suggests
ulations in which isolates cluster by geography, which led to that C. auris emerged independently and simultaneously in at
the initial identification of four distinct geographic clades: South least four geographic locations.
 4 Pathogens and Disease, 2020, Vol. 78, No. 4

Candida auris exhibits several concerning features compared et al. 2018) investigating the resistance of C. auris to physio-
to other Candida species, including persistent colonization of logically relevant stresses, found that in comparison to Can-
skin and nosocomial surfaces, and ability to resist common dis- dida albicans, C. auris is relatively resistant to hydrogen peroxide,
infectants and to survive for weeks on surfaces (Larkin et al. 2017; cationic stress and cell-wall-damaging agents, but acutely sen-
Welsh et al. 2017; Sekyere 2018; Spivak and Hanson 2018; Fors- sitive to organic oxidative-stress-inducing agents. Interestingly
berg et al. 2019; Jackson et al. 2019; Nett 2019; Singh et al. 2019). however, in contrast to other Candida species, C. auris was unable
Despite implementation of countermeasures to limit coloniza- to grow in an anaerobic environment. Combined, these find-
tion and infections in intensive care units and long-term care ings from the study indicated that C. auris has a unique stress
facilities, cases continue to be reported, reflecting the ability of resistance profile, and identified a role of Hog1 stress-activated
C. auris to persist in the clinical environment (Welsh et al. 2017; protein kinase (SAPK) in promoting stress resistance and vir-
Rossato and Colombo 2018; Cortegiani et al. 2019). Most striking ulence in this species. Another distinctive property described
however, is the efficient person-to-person transmission, which for C. auris is that it demonstrates thermotolerance, growing
is surprising as candidiasis caused by other species typically optimally at 37◦ C, and maintaining viability up to 42◦ C (Bidaud,
arises from the patient’s own microbiome (de Cássia Orlandi Chowdhary and Dannaoui 2018; Forsberg et al. 2019; Jackson et al.
Sardi et al. 2018; Spivak and Hanson 2018; de Jong and Hagen 2019). In addition to temperature, and in contrast to other Can-
2019). In contrast, C. auris does not appear to efficiently colonize dida species, C. auris can also tolerate hypersaline environments
the gastrointestinal tract (Nett 2019). Resistance to multiple drug that can induce the formation of pseudohyphae-like morphol-
classes and misidentification by available commercial identifica- ogy (Jackson et al. 2019; Kean et al. 2020).
tion systems has complicated clinical management and detec- Unlike C. albicans, morphological switching between a yeast
tion, and outcomes of infection have generally been poor with and hyphal form, a property that is central to C. albicans patho-
mortality rates approaching 68% (Larkin et al. 2017; de Jong and genesis, is not utilized by C. auris (Larkin et al. 2017; Day et al.
Hagen 2019; Nett 2019; Wickes 2020). 2018). Microscopically, C. auris isolates are ovoid budding yeast
Due to its transmissibility and high levels of antifungal resis- and are germ tube negative (Bidaud, Chowdhary and Dannaoui
tance, C. auris is now the first fungal pathogen categorized as 2018) (Fig. 2A). However, although considered incapable of fila-
a public health threat by the Centers for Disease Control and mentation in response to cues that induce C. albicans filamen-
Prevention (CDC) (Johnson et al. 2018; Forsberg et al. 2019; Nett tation, a study by Yue et al. (Yue et al. 2018) reported the dis-
2019). In June 2016, the CDC published an alert for all pub- covery of a phenotypic switching system and a temperature-
lic health authorities making it mandatory to report isolation dependent filamentous phenotype triggered by passage through
of C. auris in the USA (Bidaud, Chowdhary and Dannaoui 2018). a mammalian body. In line with these findings, more recently,
According to the CDC, the numbers of infections in the USA have Kim et al. (Kim et al. 2019) similarly reported that C. auris under-
steadily grown, and as of 31 March 31 2020, 1092 cases of C. goes a morphogenetic transition from yeast to filamentous form
auris infections have been confirmed in the USA, the majority in response to cell cycle arrest or depletion of Hsp90, which
of which have been in the New York City (Adams et al. 2018; Zhu regulates antifungal resistance and virulence. Importantly, it
and Leach 2019), New Jersey and Chicago areas (https://www.cd was also found that this developmental transition was associ-
c.gov/fungal/candida-auris/tracking-c-auris.html). Most of the ated with global transcriptional remodeling impacting cell wall-
cases were candidemias in critically-ill adults with risk factors related genes (Kim et al. 2019).
such as immunosuppression, surgery or indwelling catheters
(Cortegiani et al. 2019; de Jong and Hagen 2019; Forsberg et al.
2019). As strains have been linked to other parts of the world
Colonization and Persistence
where C. auris has been reported, it is likely that this species
was inadvertently introduced into the USA from patients who Although Candida species are typically commensals of the gas-
received healthcare in a country where C. auris was reported. trointestinal tract and not thought to spread in healthcare set-
tings, C. auris seems to have a predilection for the skin (Fors-
berg et al. 2019). To shed light on how C. auris colonize the
Pathogenesis of C. auris
skin and spread among patients, Horton et al. (Horton et al.
The ability to adapt to host-imposed stresses is crucial for the 2020) designed a porcine ex vivo skin model, and showed that
pathogenicity of fungal pathogens. Several studies have been C. auris thrives and forms high-burden multilayer biofilm struc-
performed to elucidate C. auris virulence factors, and in ani- tures on the skin surface. This capacity to efficiently colonize
mal models of disseminated infection, C. auris was shown to be the skin may explain the propensity of C. auris to persist. Sig-
as virulent as C. albicans, the most pathogenic Candida species nificantly, patients colonized with C. auris can also be a source
(Fakhim et al. 2018, Day et al. 2018; Rossato and Colombo 2018; of transmission to other patients. In fact, studies have indicated
de Jong and Hagen 2019). However, owing to its recent emer- that colonization can occur rapidly, after just a few hours or a
gence, much remains unknown about the biology and virulence few days of exposure, and patients who were colonized with
attributes of this novel pathogen (Satoh et al. 2009; Forsberg et al. C. auris developed an invasive bloodstream infection days to
2019). Interestingly, aggregative and nonaggregative phenotypes months after becoming colonized (Forsberg et al. 2019).
were recently described, the latter of which were found to be Evasion of host innate immunity is another important
more virulent in vivo (Borman, Szekely and Johnson 2016; Sherry factor that contributes to the high mortality in patients with
et al. 2017; Bidaud, Chowdhary and Dannaoui 2018). Although invasive disease. A study by Johnson et al. (Johnson et al.
some characteristics were shown to be strain-dependent, C. 2018) demonstrated that human neutrophils, not only did not
auris expresses several key virulence factors including enzymes effectively kill C. auris, but also failed to form neutrophil extra-
such as phospholipases, proteinases and secreted aspartic pro- cellular traps (NETs) upon encountering C. auris. Interestingly,
teases, as well as adhesins and the ability to form biofilms when exposed to both, neutrophils preferentially engaged and
(Kumar et al. 2015; Larkin et al. 2017; Sherry et al. 2017; Bidaud, killed C. albicans over C. auris (Johnson et al. 2018). These find-
Chowdhary and Dannaoui 2018). A study by Day et al. (Day ings are in line with those from a study by Navarro-Arias et al.
 Vila et al. 5

(Navarro-Arias et al. 2019) indicating that innate immune recog- in ergosterol content in the cellular membrane. Nevertheless,
nition of C. auris and ability to stimulate cytokine production none of these mechanisms alone can account for the high lev-
and phagocytosis, are different from that reported for C. albicans. els of resistance seen in C. auris, and multiple mechanisms are
Combined, the findings from these recent studies not only shed undoubtedly involved.
light on the pathogenesis and biology of C. auris, but seem to
indicate that this species employs unique strategies to infect, Biofilms and Drug Tolerance
persist and colonize the host (Jackson et al. 2019).
Biofilm formation and drug sequestration by the biofilm extra-
cellular matrix account for much of antifungal tolerance among
Multidrug Resistance
Candida species (Mitchell et al. 2015; Dominguez et al. 2019). Can-
The most concerning phenomenon is the unprecedented level dida auris also form biofilms, which provide a mechanism for
of drug resistance and the unique ability of C. auris to develop adherence to surfaces; however, since C. auris does not form
resistance to all three of the main classes of antifungals drug i.e. true hyphae, these biofilms are less robust and less complex
azoles, polyenes and echinocandins, severely limiting treatment than those formed by C. albicans (Forsberg et al. 2019). In ana-
options (Lockhart et al. 2017; Welsh et al. 2017; Bidaud, Chowd- lyzing the composition of C. auris biofim matrix, a study by
hary and Dannaoui 2018; de Cássia Orlandi Sardi et al. 2018; Dominguez et al. (Dominguez et al. 2019) found it to be rich in
Rossato and Colombo 2018; Spivak and Hanson 2018; Chaabane mannan-glucan polysaccharides, the main components in other
et al. 2019; Wickes 2020). In fact, the multidrug-resistant (MDR) Candida biofilm matrix. Importanty, similar to what was pre-
pattern has been frequently observed (∼40%) with serious con- viously shown with C. albicans, by tracking the penetration of
sequences for clinical and therapeutic management (Spivak and radiolabeled fluconazole through C. auris biofilms, the major-
Hanson 2018, Cortegiani et al. 2019, Forsberg et al. 2019). A large ity of the drug within the biofilm was found to be retained
study examining C. auris resistance in 350 isolates from India in the extracellular matrix, inhibited from reaching its target
identified 90% of isolates to be resistant to fluconazole (azole), (Nett 2019; Dominguez et al. 2019). Consistant with these find-
2% to anidulafungin and micafungin (echinocandins) and 8% to ings, a study comparatively evaluating antifungal susceptibilty
amphotericin B (Chowdhary, Prakash and Sharma 2018). Consis- of C. auris isolates grown plantonically vs in a biofilm demon-
tent with these findings, in the USA ∼90% of isolates were found strated that where planktonic cells were resistant to flucona-
to be resistant to fluconazole and 5% resistant to echinocandins. zole but sensitive to echinocandins and polyenes, biofilms did
Remarkably, although resistance to amphotericin B (polyene) is not show susceptibility to any antifungal agent (Romera et al.
rare in Candida species, it is observed in ∼30% of US C. auris iso- 2019). Additionally, transcriptomic analysis of temporally devel-
lates (Chaabane et al. 2019). Overall, C. auris is generally resistant oping C. auris biofilms indicated an important role for efflux-
to fluconazole, and a substantial portion of isolates are resistant mediated resistance, which may explain the tolerance of C.
to amphotericin B and echinocandins (Forsberg et al. 2019). By auris to a wide range of antimicrobial agents (Kean et al. 2018).
taking a multi-omics approach, Zamith-Miranda et al. (Zamith- Collectively, these findings highlight the importance of biofilm
Miranda et al. 2019) demonstrated that in comparison to C. albi- formation, such as those formed on intravascular catheters
cans, C. auris isolates with distinct drug susceptibility profiles (Fig. 2B) and indwelling medical devices, as a key factor under-
exhibit major differences in carbon utilization and downstream lying C. auris tolerance to antifungals.
lipid and protein content, supporting a multifactorial mecha-
nism of drug resistance. A Case of Mistaken Identity
Although antifungal resistance in C. auris was shown to be
acquired rather than intrinsic, the molecular mechanisms gov- Compounding the exponential emergence of outbreaks and high
erning drug resistance remain largely elusive (Sherry et al. 2017; rates of multi-drug resistance, C. auris has also presented lab-
Chowdhary, Prakash and Sharma 2018; Chaabane et al. 2019; oratory challenges, as it is misidentified by the most com-
Kim et al. 2019; Lockhart 2019). In fact, most of what we cur- monly used clinical microbiology methods, including biochem-
rently know has been inferred based on conservation of genes ical methods and automated testing instruments (Spivak and
associated with drug resistance in other Candida species, such Hanson 2018; de Cássia Orlandi Sardi et al. 2018). This is
as drug transporters, secreted proteases and manosyl trans- due to the phenotypic similarities with other closely related
ferases (Muñoz et al. 2018). In the ERG11 gene, which encodes the species, most notably Candida haemulonii. Accurate identification
enzyme involved in cell membrane ergosterol synthesis, three requires sophisticated methods such as matrix-assisted laser
mutations were directly linked to fluconazole-resistance in C. desorption ionization-time of flight mass spectrometry (MALDI-
albicans; these mutations were also found in C. auris, suggest- TOF MS) or DNA sequencing, which are often not available in
ing that they may similarly confer resistance in C. auris (Lock- laboratories (Wickes 2020; Cortegiani et al. 2018; Perlin 2017).
hart et al. 2017; Flowers et al. 2015). Another common mechanism However, between 2009 and 2015, using sensitive techniques,
for drug resistance in Candida species, which may contribute to restrospective studies have been able to re-identify Candida iso-
azole resistance in C. auris, is upregulation of efflux pump activ- lates as C. auris, highlighting the concerns about the challenges
ity; the extent of this contribution however, is unknown (Ben- in correct identification (Cortegiani et al. 2018; Kordalewska
Ami, Berman and Novikov 2017). Mutations in the FKS1 gene et al. 2017). The fact that its diagnosis is challenging, suggests
encoding the enzyme involved in ß-1,3-glucan synthesis in the that the spreading of C. auris is likely underestimated (Zamith-
fungal cell wall have been directly linked to echinocandin resis- Miranda et al. 2019). More concerning is that misidentification
tance in Candida species, and therefore, elevated echinocandin has resulted in inappropriate management, further complicat-
minimal inhibitory concentrations (MICs) observed in C. auris ing efforts to control the spread of C. auris in healthcare settings.
isolates are likely the result of similar mutations (Chowdhary, Therefore, rapid and reliable identification is paramount to allow
Prakash and Sharma 2018; Perlin 2015). Resistance to ampho- quick screening of patients and identification of new cases, in
tericin B however, is intriguing as it is rare, and although the order to implement appropriate infection control measures in a
mechanism is not confirmed it is probably due to a reduction timely manner (Forsberg et al. 2019).
 6 Pathogens and Disease, 2020, Vol. 78, No. 4

Breaking Bad: the Making of a Pathogen to survive on skin, axilla and groin, sites prone to high temper-
atures and high salinity (Jackson et al. 2019). Although all plau-
The most puzzling aspect of the rise of C. auris as a human sible scenarios, given our lack of knowledge about the origins of
pathogen is its inexplicable and simultaneous emergence on C. auris, it is still impossible to determine whether environmen-
five continents with genetically distinct clades, which appear tal and climactic changes were contributing factors in its recent
to have emerged independently (Lockhart et al. 2017; Nett 2019). emergence as a pathogen.
In order to determine whether C. auris was truly an emerging
human pathogen, a retrospective review of >15 000 Candida iso-
lates collected decades prior to 2009, re-identified only four iso- Perspectives and Future Directions
lates (initially identified as C. haemulonii), as C. auris (Jackson et al.
C. auris is distinct among yeast due to its transmissibility,
2019; Lockhart et al. 2017). These findings suggest that C. auris
persistence and high levels of antifungal resistance. A robust
was relatively rare before 2009, and it emerged as a cause of
response involving rapid tests for detecting patient colonization,
human infections primarily in the last decade. Although cur-
prompt interventions and implementation of precautions are
rently nothing is known about the origins C. auris, hypothe-
paramount to contain the spread of infections, particularly in
ses on its emergence have included increasing rates of anti-
hospitals and long-term care facilities. Patients potentially colo-
fungal use and human activities (Forsberg et al. 2019; Jackson
nized with C. auris, or those previously hospitalized in facilities
et al. 2019). Epidemiological characterization of C. auris cases
where C. auris was isolated, should be placed in isolation; and
found that many infected patients had been receiving antifun-
to prevent ongoing transmission, decontamination of skin and
gal drugs, suggesting that drug pressure could have resulted in
environmental surfaces and medical equipment is paramount.
the emergence of this resistant species (Lockhart et al. 2017). The
Importantly, there is a pressing need to develop coordi-
increasing access to healthcare facilities has certainly created
nated global surveillance tools among public health agencies to
opportunities for the spread of C. auris; however, other changes,
raise awareness about C. auris. Furthermore, the development
either in the organism or in the environment, might also have
of new antifungal drugs is vital to control multi-drug resistant
contributed to the emergence of this species as a serious human
isolates and prevent the increase of nosocomial infections. The
pathogen (Jackson et al. 2019).
same concerns raised with C. auris regarding its evolutionary ori-
Climate change is impacting most life on Earth, and for
gins however, apply across the microbial world. Therefore, iden-
decades, scientists have understood that the upward trends
tifying emerging disease risks is essential to ultimately optimize
in global temperatures will almost certainly bring new infec-
preventive strategies.
tious diseases, and likely lead to epidemics (Ogden and Gachon
2019). However, to predict the impact of climate on the emer-
gence of human infectious diseases requires an understand- FUNDING
ing of how microorganisms are affected by climate change and
The work in this publication was supported by the National
other human activities. The most basic assumption is that as
Institute of Allergy and Infectious Diseases of the NIH under
some microbes can adapt to higher temperatures, global warm-
award number R01AI130170 (NIAID) to MAJ-R
ing will select for those with higher heat tolerance (Ogden and
Gachon 2019; Garcia-Solache and Casadevall 2010). In addition Conflicts of Interest. None declared.
to a complex immune system, the relativey high resistance of
mammals to fungal infections is attributed to endothermy, or
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