Experimental Induction of Fluconazole Resistance in Candida tropicalis ATCC 750
Open accessAbstract
Candida tropicalis is less commonly isolated from clinical specimens than Candida albicans. Unlike C. albicans, which can be occasionally found as a commensal, C. tropicalis is almost always associated with the development of fungal infections. In addition, C. tropicalis has been reported to be resistant to fluconazole (FLC). To analyze the development of FLC resistance in C. tropicalis, an FLC-susceptible strain (ATCC 750) (MIC = 1.0 microg/ml) was cultured in liquid medium containing increasing FLC concentrations from 8.0 to 128 microg/ml. The strain developed variable degrees of FLC resistance which paralleled the concentrations of FLC used in the medium. The highest MICs of FLC were 16, 256, and 512 microg/ml for strains grown in medium with 8.0, 32, and 128 microg of FLC per ml, respectively. Development of resistance was rapid and could be observed already after a single subculture in azole-containing medium. The resistant strains were cross-resistant to itraconazole (MIC > 1.0 microg/ml) and terbinafine (MIC > 512 microg/ml) but not to amphotericin B. Isolates grown in FLC at concentrations of 8.0 and 32 microg/ml reverted to low MICs (1.0 microg/ml) after 12 and 11 passages in FLC-free medium, respectively. The MIC for one isolate grown in FLC (128 microg/ml) (128 R) reverted to 16 microg/ml but remained stable over 60 passages in FLC-free medium. Azole-resistant isolates revealed upregulation of two different multidrug efflux transporter genes: the major facilitators gene MDR1 and the ATP-binding cassette transporter CDR1. The development of FLC resistance in vitro correlated well with the results obtained in an experimental model of disseminated candidiasis. While FLC given at 10 mg/kg of body weight/day was effective in reducing the fungal burden of mice infected with the parent strain, the same dosing regimen was ineffective in mice infected with strain 128 R. Finally, the acquisition of in vitro FLC resistance in strain 128 R was related to a loss of virulence. The results of our study elucidate important characteristics and potential mechanisms of FLC resistance in C. tropicalis.
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In vitro induced resistance in C. tropicalis unveiled increased expression of CDR1 and MDR1, but there is no conclusive proof that these mechanisms act in clinical isolates.
“In addition, in vitro induced resistance unveiled the presence of increased expression of multidrug transporter genes of two different families, the ABC transporters and the major facilitators, CDR1 and MDR1, respectively. Yet, there is no conclusive proof that these mechanisms are acting in clinical isolates [91].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [91]
Previous studies with C. albicans, C. dubliniensis, and C. tropicalis demonstrated that resistance to fluconazole can be promoted following repeated in vitro exposure to the drug.
“Previous studies with C. albicans (38), C. dubliniensis (59), and C. tropicalis (9) demonstrated that resistance to fluconazole can be promoted following repeated in vitro exposure to the drug.”
From Transcriptional profiling of azole-resistant Candida parapsilosis strains (2011) · cites this paper as [9]
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- Authors
- Barchiesi, F., Calabrese, D., Sanglard, D., Falconi Di Francesco, L., Caselli, F., Giannini, D., Giacometti, A., Gavaudan, S., & Scalise, G.
- Affiliations
- <!--label omitted: 1-->Istituto di Malattie Infettive e Medicina Pubblica, Università degli Studi di Ancona, Ancona, Italy1;
- Centre Hospitalier Universitaire Vaudois (CH)
- Istituto Zooprofilattico Sperimentale dell'Umbria e delle Marche (IT)
- ORCID
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2000-06
- Volume
- 44
- Issue
- 6
- Pages
- 1578-1584
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC89916
- OpenAlex
- W2160897556
- Cited by
- 145
- References
- 41
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 2 · 2018: 8 · 2017: 9 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 7 · 2012: 6
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida tropicalis, fluconazole resistance, antifungal resistance, multidrug efflux transporter, MDR1, CDR1, systemic candidiasis, antifungal susceptibility, Candida albicans comparison, experimental infection in mice
- MeSH terms
- Animals, Candida, Drug Resistance, Microbial, Virulence, Fluconazole, Gene Expression Regulation, Fungal, Mice
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