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Persistence and spread of fluconazole-resistant Candida parapsilosis clinical isolates associated with increased ERG11 copies in Qatar
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PRE
AI
张
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DOI：10.1099/mgen.0.001653.png)
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Abstract
En 中文
Candida parapsilosis is one of the most common species associated with candidemia infections globally. Recently, the emergence of fluconazole- resistant (FLU- R) C. parapsilosis has become a significant global public health concern. In this study, we investigated the genomic epidemiology and potential mechanisms of antifungal resistance among 51 hospital isolates in Qatar, of which 18 were FLU- R. Whole- genome SNP analysis revealed the presence of five major genetic clusters and evidence for cross- hospital transmission within clusters I, II and III. Cluster I had 21 isolates, including all 18 FLU- R isolates collected from 2015 to 2021. These 18 FLU- R isolates had no missense variants known to be associated with azole resistance in loci such as ERG11, ERG6 and TAC1; however, all FLU- R isolates had increased copy numbers of ERG11, ranging from 3 to 7 copies. In addition, most FLU- R isolates (n=16) had increased CDR1B copies (2-8 copies). These FLU- R isolates also had higher expression of ERG11 and CDR1B than sensitive strains. A genome- wide association study revealed 16 variants in several loci of unknown function that may be linked to resistance to FLU and 5- flucytosine. All cluster I isolates had unique missense mutations in EFG1 and UME6 that may play important roles in morphogenesis and biofilm formation. Our findings indicate these cluster I isolates may have evolved a greater propensity to persist within hospitals for prolonged periods and cause clonal transmission than isolates in other genetic clusters susceptible to fluconazole.
Keywords:
azole resistance
candidemia
copy number variation
gene expression
nosocomial
molecular
Middle East
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