Emergence of the Novel SixthCandida aurisClade 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: April 2024

ABSTRACTCandida 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 ofC. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis ofC. aurisfrom Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. TenC. aurisisolates collected from hospital settings in Bangladesh were initially identified by CHROMagar™ Candida Plus, followed by VITEK®2 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 IC. aurisB11205 reference genome. Of the ten isolates, eight 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 SNP differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) ofC. aurisin Bangladesh, with potential for international transmission. AFST results showed that 80% of theC. aurisisolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealedERG11_Y132F mutation conferring azole resistance whileFCY1_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 ofC. aurisinfections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida aurisis a nosocomial fungal pathogen which is commonly misidentified as otherCandidaspecies. Since its emergence in 2009, this multi-drug resistant fungus has become one of the five urgent antimicrobial threat by 2019. Whole Genome Sequencing (WGS) has proven to be the most accurate identification technique ofC. auriswhich also played a crucial role in the initial discovery of this pathogen. WGS analysis ofC. aurishas 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. auriswas 1streported in 2019 from clinical samples of a large hospital of Dhaka city. To understand the origin, transmission dynamics and antifungal resistance profile ofC. aurisisolates circulating in Bangladesh, we conducted WGS based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.