Evidence map›Paper›PMID 41724950›Full record

ArticleJournal of biomedical science2026

Genetic variation and mutational determinants of azole resistance in Candida albicans strains of oropharyngeal colonization in HIV patients and bloodstream infections.

Ming-Horng Tsai, Chih-Hung Hsieh, I-An Tsai, Ching-Min Chang, Ting-Wen Chen, Jen-Fu Hsu, Shih-Ming Chu, Hsuan-Rong Huang, Shao-Hung Wang, Jang-Jih Lu

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Article in Journal of biomedical science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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10 authors.

Ming-Horng TsaiDivision of Neonatology and Pediatric Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Yunlin, Taiwan.
Chih-Hung HsiehInstitute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan.
I-An TsaiDivision of Neonatology and Pediatric Hematology/Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Yunlin, Taiwan.
Ching-Min ChangCollege of Medicine, Chang Gung University, Taoyuan, Taiwan.
Ting-Wen ChenInstitute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University, Hsinchu, 300, Taiwan.
Jen-Fu HsuCollege of Medicine, Chang Gung University, Taoyuan, Taiwan.
Shih-Ming ChuCollege of Medicine, Chang Gung University, Taoyuan, Taiwan.
Hsuan-Rong HuangCollege of Medicine, Chang Gung University, Taoyuan, Taiwan.
Shao-Hung WangDepartment of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, 600, Taiwan. shwang@mail.ncyu.edu.tw.
Jang-Jih LuDivision of Clinical Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, 23142, Taiwan. janglu45@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesWe aimed to analyze the genomic variations associated with high azole resistance in the C. albicans isolates of intensive care unit (ICU) patients with Candida bloodstream infections (BSIs) and those from oropharyngeal colonization in HIV patients.

methodsThe genomic DNA of azole-resistant C. albicans isolates was analyzed using the Oxford Nanopore platform. Subsequent analyses included ERG11 alignment to determine the extent and distribution of missense substitutions, Ka/Ks calculations to test for positive selection on ERG11, and detailed CDR1 and CDR2 mutational analysis across the coding sequence. Efflux function was assessed by measuring the fold reduction in the minimum inhibitory concentration (MIC) of azole drugs in the presence of milbemycin.

resultsA total of 27 azole-resistant C. albicans isolates from ICU patients with Candida BSIs in Linkou Chang Gung Memorial Hospital in Taiwan and HIV patients' oropharyngeal colonization were identified and analyzed. The in-depth, core analyses were performed on seven representative C. albicans isolates. The C. albicans isolates of HIV-infected patients had notably higher azole resistance (fluconazole MICs > 256 mg/L) when compared with those of the ICU patients (fluconazole MICs 16-64 mg/L), suggesting the involvement of additional mechanisms. The central role of ERG11 mutations was supported by the presence of ERG11 missense mutations in all azole-resistant C. albicans isolates. The ERG11 coding regions analyses showed no evidence of positive selection (Ka/Ks < 1.0) and no specific mutation unique to the C. albicans isolates of the HIV patients, but unique missense mutations only in CDR1/CDR2 were noted. Milbemycin substantially decreased the azole MICs in all C. albicans isolates and confirmed the efflux pump involvement. The effects of milbemycin were much lower in C. albicans of the HIV patients than those from the ICU patients. Furthermore, unique ERG11 promoter variants, including changes at the Hap43p/Hap5p sites, were noted in the C. albicans isolates of the HIV patients.

conclusionsWhile ERG11 structural mutations are foundational, the elevated azole resistance in the C. albicans isolates of HIV-infected patients is associated with specific CDR1/CDR2 mutations and distinct ERG11 promoter variants, highlighting genomic features that warrant further functional validation.

Indexed as

Antifungal AgentsAzolesCandida albicansCandidiasisDrug Resistance, FungalGenetic VariationHIV InfectionsFemaleFungal ProteinsHumansMicrobial Sensitivity TestsMutationOropharynxAntifungal AgentsAzolesFungal ProteinsAntifungal susceptibility testingAzoles resistanceCandida albicansCandida bloodstream infectionERG11 efflux genes

Identifiers

PMID41724950
PMCPMC12925357

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.