article · Antimicrobial Agents and Chemotherapy
Analysis of Candida glabrata isolates collected from hospitalised patients in Japan between 1997 and 2019 identified the molecular patterns underlying antifungal resistance. Caspofungin resistance appeared in 32.6 percent of isolates, while micafungin resistance reached 4.7 percent. Resistance rates to azole antifungals were lower, spanning 2.3 percent to 9.3 percent, and flucytosine non-wild-type susceptibility was found in 4.7 percent of samples. Additionally, 4.7 percent of the isolates exhibited multidrug resistance, marking the first documented cases in Japan. Genetic sequencing linked azole resistance to nonsynonymous mutations in the PDR1 gene, including two newly discovered mutations, alongside a single ERG11 mutation. Echinocandin resistance was tied to mutations in hotspot 1 of the FKS1 and FKS2 genes. Multilocus sequence typing detected 13 sequence types, three of which were newly observed. Sequence type 7 was the most common lineage, representing 35 percent of cases and displaying high resistance rates.
Fungal infections caused by Candida glabrata are increasingly difficult to manage due to rising resistance against standard treatments such as azoles and echinocandins. Uncovering the exact genetic mutations that cause resistance, alongside tracking high-risk fungal lineages in hospitals, helps clinicians select appropriate targeted therapies for patients and aids infection control teams in preventing the hospital spread of multidrug-resistant strains.
This early-stage research identifies specific genetic markers that could assist diagnostic developers and pathology laboratories in designing molecular screening tools for antifungal resistance in Candida glabrata. Such tools could help guide hospital treatment strategies, though the work is currently observational and laboratory-based, requiring further validation and assay development before reaching clinical or commercial deployment.
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Infections caused by <i>Candida glabrata</i> have caused worldwide concern, especially when they are associated with increasing echinocandin and azole resistance. In this study, we analyzed the molecular mechanisms of azole and echinocandin resistance in <i>C. glabrata</i> isolates obtained from hospitalized patients in Japan from 1997 to 2019. All isolates were checked phenotypically for resistance and genotypically for mutations in <i>PDR1</i>, <i>ERG11</i>, hot spot 1 (HS1), HS2, and HS3 of <i>FKS1</i>, and HS1 and HS2 of <i>FKS2</i>, and all isolates were genotyped by multilocus sequence typing (MLST). Interestingly, 32.6% of the isolates were resistant to caspofungin, and 4.7% were resistant to micafungin. The isolates showed low rates of resistance to azoles, ranging from 2.3% to 9.3%, and only 4.7% of the isolates were non-wild type for flucytosine susceptibility. For the first time in Japan, 4.7% of the isolates were identified as multidrug-resistant strains. Nonsynonymous mutations in <i>PDR1</i>, including two novel mutations associated with azole resistance, were identified in 39.5% of the isolates, and a single nonsynonymous mutation was identified in <i>ERG11</i> Nine isolates from the same patient harbored nonsynonymous mutations in HS1 of <i>FKS2</i>, and a single isolate harbored a single nonsynonymous mutation in HS1 of <i>FKS1</i> MLST genotyping revealed 13 different sequence types (STs), with 3 new STs, and ST7 was the most prevalent among the patients (35%) and was associated with high resistance rates. Our results are of crucial clinical concern, since understanding the molecular mechanisms underlying fungal resistance is imperative for guiding specific therapy for efficient patient treatment and promoting strategies to prevent epidemic spread.
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DOI: 10.1128/aac.00783-20
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