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Updated: Oct 9, 2026
Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Regional expansion and adaptive evolution of multidrug-resistant Candida tropicalis in China: a retrospective,
Chendi Zhu1, Min Zhang2, Feifei Wan3
1Department of Laboratory Medicine, Shanghai East Hospital, Key Laboratory of Pathogen-Host Interaction (Tongji University), Ministry of Education, Shanghai, China; Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Background:
The emergence of antifungal-resistant Candida tropicalis poses a severe threat to human health and complicates clinical management, yet the molecular epidemiology and mechanisms underlying its resistance and persistence in hospital settings remain poorly understood. We aimed to investigate the regional epidemiology, persistence and virulence trade-offs, and adaptive traits associated with the expansion of multidrug-resistant C tropicalis.
Methods:
We conducted a retrospective, multicentre, genomic study of C tropicalis isolates from 84 hospitals in east China and included additional multidrug-resistant (resistant to azoles and echinocandins) isolates from active surveillance at Shanghai East Hospital. We analysed clinical metadata from this hospital to identify risk factors for multidrug-resistant isolate recovery and 30-day mortality. We conducted whole-genome sequencing, RNA sequencing, phenotypic assays, and experimental evolution to elucidate resistance mechanisms, virulence dynamics, and adaptive traits.
Findings:
1184 clinical isolates from Jan 1, 2017, to Dec 31, 2024, were included; of these, 356 (30·1%) were azole resistant and 98 (8·3%) were multidrug resistant. We identified the regional expansion of a multidrug-resistant C tropicalis lineage, DST849, which accounted for 92 (94%) of 98 multidrug-resistant cases and was predominantly isolated from the urinary tract. Admission to a surgical ward (adjusted odds ratio [aOR] 46·37, 95% CI 17·48-123·00) and intubation (32·30, 10·28-101·45) were key risk factors for multidrug-resistant isolate recovery. Multivariable logistic regression revealed that multidrug-resistant C tropicalis isolation was an independent predictor of 30-day mortality (aOR 2·84, 95% CI 1·31-6·16; p=0·0081). Phylogenomic analysis revealed that multidrug-resistant isolates evolved from azole-resistant ancestors (DST225) via the acquisition of FKS1 mutations (S30P) while retaining ERG11 mutations (Y132F and S154F) and acquired a distinguishing ICL1 (Y43T) loss-of-heterozygosity mutation.
Interpretation:
Our findings reveal the emergence of multidrug-resistant Ctropicalis through lineage-specific expansion, driven by genetic plasticity and adaptive stress responses. These adaptations might facilitate persistence under antifungal and environmental pressures in health-care settings. These insights underscore the urgent need for improved antifungal stewardship, targeted genomic surveillance, and interventions to mitigate multidrug-resistant fungal threats.
Funding:
National Natural Science Foundation of China, Chinese Ministry of Science and Technology.
