Emergence of the novel sixth
Candida auris
Clade VI in Bangladesh
Authors: Khan Tahsin , Faysal Naimul Islam , Hossain Md Mobarok , Mah-E-Muneer Syeda , Haider Arefeen , Moon Shovan Basak , Sen Debashis , Ahmed Dilruba , Parnell Lindsay A. , Jubair Mohammad , Chow Nancy A. , Chowdhury Fahmida , Rahman Mustafizur 
Published: June 2024

ABSTRACT

Candida auris
, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of
C. auris
, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of
C. auris
from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten
C. auris
isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I
C. auris
B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of
C. auris
in Bangladesh, with potential for international transmission. AFST results showed that 80% of the
C. auris
isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed
ERG11
_Y132F mutation conferring azole resistance while
FCY1
_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of
C. auris
infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.

IMPORTANCE

Candida auris
is a nosocomial fungal pathogen that is commonly misidentified as other
Candida
species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of
C. auris
which also played a crucial role in the initial discovery of this pathogen. WGS analysis of
C. auris
has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh,
C. auris
was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of
C. auris
isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.