ArticleFrontiers in microbiology2016
Clotrimazole Drug Resistance in Candida glabrata Clinical Isolates Correlates with Increased Expression of the Drug:H(+) Antiporters CgAqr1, CgTpo1_1, CgTpo3, and CgQdr2.
Article in Frontiers in microbiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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28 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
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- Genomic Analysis Reveals Diversified and Stress-Responsive Transport Repertoire inJournal of fungi (Basel, Switzerland) · 2026Article
- Salvianolic acid B synergizes with azoles againstFrontiers in cellular and infection microbiology · 2026Article
- Temporal transcriptional response ofeLife · 2024Article
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- Multiple genome analysis ofMicrobial cell (Graz, Austria) · 2022Article
- Genomic evolution towards azole resistance in Candida glabrata clinical isolates unveils the importance of CgHxt4/6/7 in azole accumulation.Communications biology · 2022Article
- Genomic Data Mining Reveals Abundant Uncharacterized Transporters inJournal of fungi (Basel, Switzerland) · 2022Article
- Probiotics Reduce Vaginal Candidiasis in Pregnant Women via Modulating Abundance ofMicroorganisms · 2022Article
- Susceptibility to Clotrimazole ofPathogens (Basel, Switzerland) · 2021Article
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- An Overview on Conventional and Non-Conventional Therapeutic Approaches for the Treatment of Candidiasis and Underlying Resistance Mechanisms in Clinical Strains.Journal of fungi (Basel, Switzerland) · 2020Review
- Screening the Drug:HFrontiers in cellular and infection microbiology · 2020Article
- Draft Genome Sequences of Three Clinical Isolates of the Pathogenic Yeast Candida glabrata.Microbiology resource announcements · 2019Article
- Clotrimazole-Loaded Mediterranean Essential Oils NLC: A Synergic Treatment ofPharmaceutics · 2019Article
- Decreasing Cell Population of IndividualFrontiers in microbiology · 2019Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
For years, antifungal drug resistance in Candida species has been associated to the expression of ATP-Binding Cassette (ABC) multidrug transporters. More recently, a few drug efflux pumps from the Drug:H(+) Antiporter (DHA) family have also been shown to play a role in this process, although to date only the Candida albicans Mdr1 transporter has been demonstrated to be relevant in the clinical acquisition of antifungal drug resistance. This work provides evidence to suggest the involvement of the C. glabrata DHA transporters CgAqr1, CgQdr2, CgTpo1_1, and CgTpo3 in the clinical acquisition of clotrimazole drug resistance. A screening for azole drug resistance in 138 C. glabrata clinical isolates, from patients attending two major Hospitals in Portugal, was performed. Based on this screening, 10 clotrimazole susceptible and 10 clotrimazole resistant isolates were selected for further analysis. The transcript levels of CgAQR1, CgQDR2, CgTPO1_1, and CgTPO3 were found to be significantly up-regulated in resistant isolates when compared to the susceptible ones, with a level of correlation that was found to be similar to that of CgCDR2, an ABC gene known to be involved in the clinical acquisition of resistance. As a proof-of-concept experiment, the CgTPO3 gene was deleted in an azole resistant C. glabrata isolate, exhibiting high levels of expression of this gene. The deletion of CgTPO3 in this isolate was found to lead to decreased resistance to clotrimazole and fluconazole, and increased accumulation of azole drugs, thus suggesting the involvement of this transporter in the manifestation of azole resistance.
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