Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study
Background: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in...
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Medicine, Health and Life Sciences Candida auris Singapore Suphavilai, Chayaporn Ko, Karrie Kwan Ki Lim, Kar Mun Tan, Mei Gie Boonsimma, Patipan Chu, Joash Jun Keat Goh, Sui Sin Rajandran, Prevena Lee, Lai Chee Tan, Kwee Yuen Bushra Binte Shaik Ismail Aung, May Kyawt Yang, Yong Sim, Jean Xiang Ying Venkatachalam, Indumathi Cherng, Benjamin Pei Zhi Spruijtenburg, Bram Chan, Kian Sing Oon, Lynette Lin Ean Tan, Ai Ling Tan, Yen Ee Wijaya, Limin Tan, Ban Hock Ling, Moi Lin Koh, Tse Hsien Meis, Jacques F. Tsui, Clement Kin Ming Nagarajan, Niranjan Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study |
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Background: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I–V). Methods: In this genotypic and phenotypic study, we characterised three C auris clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these C auris isolates. The complete genomes were compared with representative genomes of all known C auris clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available. Findings: The three investigated isolates were separated by at least 37 000 SNPs (range 37 000–236 900) from all existing C auris clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of C auris, clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade. Interpretation: The discovery of a new C auris clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of C auris, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of C auris infections. |
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Lee Kong Chian School of Medicine (LKCMedicine) |
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Lee Kong Chian School of Medicine (LKCMedicine) Suphavilai, Chayaporn Ko, Karrie Kwan Ki Lim, Kar Mun Tan, Mei Gie Boonsimma, Patipan Chu, Joash Jun Keat Goh, Sui Sin Rajandran, Prevena Lee, Lai Chee Tan, Kwee Yuen Bushra Binte Shaik Ismail Aung, May Kyawt Yang, Yong Sim, Jean Xiang Ying Venkatachalam, Indumathi Cherng, Benjamin Pei Zhi Spruijtenburg, Bram Chan, Kian Sing Oon, Lynette Lin Ean Tan, Ai Ling Tan, Yen Ee Wijaya, Limin Tan, Ban Hock Ling, Moi Lin Koh, Tse Hsien Meis, Jacques F. Tsui, Clement Kin Ming Nagarajan, Niranjan |
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Article |
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Suphavilai, Chayaporn Ko, Karrie Kwan Ki Lim, Kar Mun Tan, Mei Gie Boonsimma, Patipan Chu, Joash Jun Keat Goh, Sui Sin Rajandran, Prevena Lee, Lai Chee Tan, Kwee Yuen Bushra Binte Shaik Ismail Aung, May Kyawt Yang, Yong Sim, Jean Xiang Ying Venkatachalam, Indumathi Cherng, Benjamin Pei Zhi Spruijtenburg, Bram Chan, Kian Sing Oon, Lynette Lin Ean Tan, Ai Ling Tan, Yen Ee Wijaya, Limin Tan, Ban Hock Ling, Moi Lin Koh, Tse Hsien Meis, Jacques F. Tsui, Clement Kin Ming Nagarajan, Niranjan |
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Suphavilai, Chayaporn |
title |
Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study |
title_short |
Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study |
title_full |
Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study |
title_fullStr |
Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study |
title_full_unstemmed |
Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study |
title_sort |
detection and characterisation of a sixth candida auris clade in singapore: a genomic and phenotypic study |
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2024 |
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https://hdl.handle.net/10356/181384 |
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sg-ntu-dr.10356-1813842024-12-01T15:39:47Z Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study Suphavilai, Chayaporn Ko, Karrie Kwan Ki Lim, Kar Mun Tan, Mei Gie Boonsimma, Patipan Chu, Joash Jun Keat Goh, Sui Sin Rajandran, Prevena Lee, Lai Chee Tan, Kwee Yuen Bushra Binte Shaik Ismail Aung, May Kyawt Yang, Yong Sim, Jean Xiang Ying Venkatachalam, Indumathi Cherng, Benjamin Pei Zhi Spruijtenburg, Bram Chan, Kian Sing Oon, Lynette Lin Ean Tan, Ai Ling Tan, Yen Ee Wijaya, Limin Tan, Ban Hock Ling, Moi Lin Koh, Tse Hsien Meis, Jacques F. Tsui, Clement Kin Ming Nagarajan, Niranjan Lee Kong Chian School of Medicine (LKCMedicine) Tan Tock Seng Hospital National Centre for Infectious Diseases Medicine, Health and Life Sciences Candida auris Singapore Background: The emerging fungal pathogen Candida auris poses a serious threat to global public health due to its worldwide distribution, multidrug resistance, high transmissibility, propensity to cause outbreaks, and high mortality. We aimed to characterise three unusual C auris isolates detected in Singapore, and to determine whether they constitute a novel clade distinct from all previously known C auris clades (I–V). Methods: In this genotypic and phenotypic study, we characterised three C auris clinical isolates, which were cultured from epidemiologically unlinked inpatients at a large tertiary hospital in Singapore. The index isolate was detected in April, 2023. We performed whole-genome sequencing (WGS) and obtained hybrid assemblies of these C auris isolates. The complete genomes were compared with representative genomes of all known C auris clades. To provide a global context, 3651 international WGS data from the National Center for Biotechnology Information (NCBI) database were included in a high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal susceptibility testing was done and antifungal resistance genes, mating-type locus, and chromosomal rearrangements were characterised from the WGS data of the three investigated isolates. We further implemented Bayesian logistic regression models to classify isolates into known clades and simulate the automatic detection of isolates belonging to novel clades as their WGS data became available. Findings: The three investigated isolates were separated by at least 37 000 SNPs (range 37 000–236 900) from all existing C auris clades. These isolates had opposite mating-type allele and different chromosomal rearrangements when compared with their closest clade IV relatives. The isolates were susceptible to all tested antifungals. Therefore, we propose that these isolates represent a new clade of C auris, clade VI. Furthermore, an independent WGS dataset from Bangladesh, accessed via the NCBI Sequence Read Archive, was found to belong to this new clade. As a proof-of-concept, our Bayesian logistic regression model was able to flag these outlier genomes as a potential new clade. Interpretation: The discovery of a new C auris clade in Singapore and Bangladesh in the Indomalayan zone, showing a close relationship to clade IV members most commonly found in South America, highlights the unknown genetic diversity and origin of C auris, particularly in under-resourced regions. Active surveillance in clinical settings, along with effective sequencing strategies and downstream analysis, will be essential in the identification of novel strains, tracking of transmission, and containment of adverse clinical effects of C auris infections. Published version This work was supported by the Duke-NUS Academic Medical Center Academic Clinical Program Nurturing Clinician Researcher Scheme (grant number 09/FY2022/P1/17-A32, GRDUKP003401), the Genedant-GIS Innovation Program grant, resources from the Genome Institute of Singapore, and resources from Singapore General Hospital. KKKK is supported by the Singapore National Medical Research Council research training fellowship (MOH-FLWSHP19may-0005). The work was supported in part through computational resources (Sockeye) and services provided by Advanced Research Computing at the University of British Columbia, Vancouver, BC, Canada. 2024-11-27T07:20:12Z 2024-11-27T07:20:12Z 2024 Journal Article Suphavilai, C., Ko, K. K. K., Lim, K. M., Tan, M. G., Boonsimma, P., Chu, J. J. K., Goh, S. S., Rajandran, P., Lee, L. C., Tan, K. Y., Bushra Binte Shaik Ismail, Aung, M. K., Yang, Y., Sim, J. X. Y., Venkatachalam, I., Cherng, B. P. Z., Spruijtenburg, B., Chan, K. S., Oon, L. L. E., ...Nagarajan, N. (2024). Detection and characterisation of a sixth Candida auris clade in Singapore: a genomic and phenotypic study. The Lancet Microbe, 5(9), 100878-. https://dx.doi.org/10.1016/S2666-5247(24)00101-0 2666-5247 https://hdl.handle.net/10356/181384 10.1016/S2666-5247(24)00101-0 39008997 2-s2.0-85198548710 9 5 100878 en 09/FY2022/P1/17-A32 GRDUKP003401 The Lancet Microbe © 2024 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). application/pdf |