Mutants with heteroresistance to amphotericin B and fluconazole in Candida
Open accessAbstract
Several studies have reported the occurrence of infections caused by Candida yeasts as well as the increasing prevalence of non albicans species. The aim of the present work is focused on the obtaining of heteroresistance to amphotericin B and fluconazole in Candida species using two distinct methodologies: selection and induction. Resistant samples were obtained by selective pressure using a medium with fluconazole for growth, followed by growth in a medium with amphotericin B. The selective pressure was also created beginning with growth in amphotericin B medium followed by growth in fluconazole medium. Concomitantly, samples were submitted to the induction of resistance through cultivation in increasing concentrations of fluconazole, followed by cultivation in increasing concentrations of amphotericin B. Subsequently, the induction began with amphotericin B followed by fluconazole. Three samples resistant to fluconazole and amphotericin B were obtained, two by induction (C. glabrata and C. tropicalis) and one by selection (C. tropicalis). Both C. tropicalis originated from the same wild sample. After successive transfers for drug free medium, only the sample obtained by selection was able to maintain the resistance phenotype. These results suggest that the phenotype of heteroresitance to fluconazole and amphotericin B can be produced by two methodologies: selection and induction.
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Heteroresistance may be induced by pharmacological factors or non-pharmacological agents.
“Heteroresistance may be induced by pharmacological factors or non-pharmacological agents.”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [101]
The Abstract and Discussion report that antifungal-drug exposure can induce or select heteroresistance in Candida. They do not establish that non-pharmacological agents induce heteroresistance; the Discussion mentions other factors in the selection of non-albicans species, which is a different point. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSeveral studies have confirmed increased emergence of heteroresistance in clinical compared with environmental isolates.
“Several studies have confirmed the increased emergence of heteroresistance in clinical, compared with environmental, isolates, supporting the induction effect of antifungal exposure [101,158].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [101]
The Discussion reports that prior fluconazole exposure may produce heteroresistant strains, supporting the sentence’s point about antifungal exposure. Neither the Discussion nor the Introduction compares the emergence of heteroresistance in clinical versus environmental isolates, so the claimed difference is unsupported by this paper. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIncreased emergence of heteroresistance in clinical versus environmental isolates supports the induction effect of antifungal exposure.
“Several studies have confirmed the increased emergence of heteroresistance in clinical, compared with environmental, isolates, supporting the induction effect of antifungal exposure [101,158].”
From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [101]
The Materials and Methods describe testing 30 clinical isolates, and the Discussion reports heteroresistance produced through antifungal exposure. The paper does not compare clinical with environmental isolates or establish that heteroresistance emerges more often in clinical isolates. (LLM, conf=0.86)
Experimental — accuracy not yet measuredC. glabrata subpopulations originating from a clonal population can develop heteroresistance to fluconazole through transient upregulation of efflux pumps.
“studies have demonstrated the ability of C. glabrata subpopulations originating from a clonal population to develop heteroresistance to fluconazole through transient upregulation of efflux pumps (Claudino et al., 2009; Ben-Ami et al., 2016).”
From Genetic Drivers of Multidrug Resistance in Candida glabrata (2016) · cites this paper as Claudino et al., 2009
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- Authors
- Claudino, A. L. R., Peixoto Junior, R. F., Melhem, M. S. C., Szeszs, M. W., Lyon, J. P., Chavasco, J. K., & Franco, M. C.
- Affiliations
- Universidade Federal de Alfenas (BR)
- Instituto Adolfo Lutz (BR)
- Universidade do Vale do Paraíba (BR)
- Venue
- Brazilian Journal of Microbiology
- Publisher
- FapUNIFESP (SciELO)
- Published
- 2009-12
- Volume
- 40
- Issue
- 4
- Pages
- 943-951
- ISSN
- 1517-8382 (ISSN-L)
- PMC
- PMC3768567
- OpenAlex
- W1970251610
- Cited by
- 12
- References
- 31
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2012: 1
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Brazilian Journal of Microbiology (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
- Americanae (AECID Library) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- Candida, heteroresistance, amphotericin B, fluconazole, antifungal resistance, Candida tropicalis, Candida glabrata, resistance selection, induced resistance, non-albicans Candida
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