Sixth major Candida auris clade discovered

Researchers have found a new clade of Candida (C) auris, a multidrug-resistant fungal pathogen, in a genotypic and phenotypic study.

Five geographically distinct C auris clades have been described: clade I (South Asian), clade II (East Asian), clade III (African), clade IV (South American), and clade V (Iranian). [Emerg Microbes Infect 2022;11:2405-2411; Clin Infect Dis 2017;64:134-140] These clades varied in terms of clinical manifestations, antifungal susceptibility profiles, and capabilities to spread. [J Infect Chemother 2019;25:743-749]

“We report the discovery of a proposed sixth major clade of C auris, which includes three epidemiologically unlinked isolates detected in Singapore and one isolate reported from Bangladesh,” said the researchers.

The SG isolates

Three C auris clinical isolates (A, B, and C) were cultured from inpatients at the Singapore General Hospital (SGH). Separated by at least 37,000 single nucleotide polymorphisms from all existing C auris clades, these isolates had opposing mating-type allele and different chromosomal rearrangements when compared against their closest clade IV relatives. [Lancet Microbe 2024;5:100878]

“[As they] were susceptible to all tested antifungals … we propose that these isolates represent a new clade of C auris, clade VI,” the researchers said.

Isolate A (index isolate) was first detected by PCR* from a routine C auris screening swab and subsequently cultured in April 2023. The swab was taken within 24 hours of admission as part of the hospital’s C auris active surveillance programme.

Isolate B was cultured from an intraoperative tissue specimen in April 2022, while isolate C was cultured from a positive blood culture in January 2018.

Patient A had no travel history in the preceding 2 years. Patient B had outpatient visits in Indonesia in 2021 but no travel history in the preceding 2 months. Isolate C was from a patient airlifted from Bangladesh to SGH, which has been sequenced in 2019.

The Bangladesh isolate

An independent whole-genome sequencing dataset from Bangladesh, accessed via the NCBI** Sequence Read Archive, was found to belong to the new clade. As proof-of-concept, the outlier genomes were flagged as a potential new clade on Bayesian logistic regression analysis.

This discovery underlines the possibility that clade VI strains could be circulating undetected in Bangladesh, with the first documented isolate being isolate C.

A serious public health threat

“The emerging fungal pathogen C 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,” the researchers noted.

The WHO has classified C auris as a critical priority pathogen, and the US Centers for Disease Control and Prevention declared C auris as an urgent antimicrobial resistance threat, underpinning the need to understand and mitigate this public health threat. [Nat Rev Microbiol 2023;21:211-212; https://stacks.cdc.gov/view/cdc/82532, accessed December 27, 2024]

“The independent detection of clade VI isolates from Singapore and Bangladesh suggests that clade VI strains might have been circulating undetected in Southeast Asia and South Asia,” they said, adding that this underlines the unknown genetic diversity and origin of C auris, specifically 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,” the researchers concluded.