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Candida tropicalis Antifungal Cross-Resistance Is Related to Different Azole Target (Erg11p) Modifications
Open accessAbstract
Candida tropicalis ranks between third and fourth among Candida species most commonly isolated from clinical specimens. Invasive candidiasis and candidemia are treated with amphotericin B or echinocandins as first-line therapy, with extended-spectrum triazoles as acceptable alternatives. Candida tropicalis is usually susceptible to all antifungal agents, although several azole drug-resistant clinical isolates are being reported. However, C. tropicalis resistant to amphotericin B is uncommon, and only a few strains have reliably demonstrated a high level of resistance to this agent. The resistance mechanisms operating in C. tropicalis strains isolated from clinical samples showing resistance to azole drugs alone or with amphotericin B cross-resistance were elucidated. Antifungal drug resistance was related to mutations of the azole target (Erg11p) with or without alterations of the ergosterol biosynthesis pathway. The antifungal drug resistance shown in vitro correlated very well with the results obtained in vivo using the model host Galleria mellonella. Using this panel of strains, the G. mellonella model system was validated as a simple, nonmammalian minihost model that can be used to study in vitro-in vivo correlation of antifungals in C. tropicalis. The development in C. tropicalis of antifungal drug resistance with different mechanisms during antifungal treatment has potential clinical impact and deserves specific prospective studies.
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“Importantly, instances of cross-resistance towards amphortericin B and azoles or echinocandinds in Candida have also been reported [50,51,52,53].”
From Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens (2018) · cites this paper as [53]
In the citing paper
“Additionally, the latest cross-resistance between amphotericin B and azoles or caspofungin in Candida species are increasingly worrying [103,194,195,196,197].”
From Candida glabrata Biofilms: How Far Have We Come? (2017) · cites this paper as [197]
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Drug resistance and treatment failure in leishmaniasis: A 21st century challenge
Ponte‐Sucre, A., Gamarro, F., Dujardin, J., Barrett, M. P., López‐Vélez, R., García‐Hernández, R., Pountain, A. W., Mwenechanya, R., & Papadopoulou, B. (2017) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0006052 · Cited by 971
An Update on Candida tropicalis Based on Basic and Clinical Approaches
Zuza-Alves, D. L., Rocha, W. P. D. S., & Chaves, G. M. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01927 · Cited by 314
Mesa-Arango, A. C., Trevijano-Contador, N., Román, E., Sánchez-Fresneda, R., Casas, C., Herrero, E., Argüelles, J. C., Pla, J., Cuenca-Estrella, M., & Zaragoza, O. (2014) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.03570-14 · Cited by 232
Self-citationEvolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens
Ksiezopolska, E., & Gabaldón, T. (2018) · Genes · doi:10.3390/genes9090461 · Cited by 230
Fungal Cell Wall: Emerging Antifungals and Drug Resistance.
Lima, S. L., Colombo, A. L., & de Almeida Junior, J. N. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02573 · Cited by 223
“…AMB resistance has been linked to several potential mechanisms, such as increase in catalase activity, changes in mitochondrial potential, low accumulation of reactive oxygen species, and deficiency in ergosterol at the cell membrane (Forastiero et al., 2013; Mesa-Arango et al., 2014).”
Background
Metadata
- Authors
- Forastiero, A., Mesa-Arango, A. C., Alastruey-Izquierdo, A., Alcazar-Fuoli, L., Bernal-Martinez, L., Pelaez, T., Lopez, J. F., Grimalt, J. O., Gomez-Lopez, A., Cuesta, I., Zaragoza, O., & Mellado, E.
- Affiliations
- Instituto de Salud Carlos III (ES)
- Mycology Reference Laboratory, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain
- Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, and Department of Medicine, Faculty of Medicine, Universidad Complutense, Madrid, Spain
- Departamento de Química Ambiental, Institute of Environmental Assessment and Water Research (IDÆA), Consejo Superior de Investigaciones Científicas, Barcelona, Spain
- Consejo Superior de Investigaciones Científicas (ES)
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2013-10
- Volume
- 57
- Issue
- 10
- Pages
- 4769-4781
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC3811422
- OpenAlex
- W2115223992
- Cited by
- 131
- References
- 78
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 7 · 2023: 15 · 2022: 13 · 2021: 7 · 2020: 14 · 2019: 10 · 2018: 15 · 2017: 6 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 1
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repository University of Antioquia (University of Antioquia) (submittedVersion, cc-by)
- 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 › Plant Science › Fungal Plant Pathogen Control
- Keywords
- Candida tropicalis, antifungal resistance, azole resistance, cross-resistance, amphotericin B resistance, ergosterol biosynthesis, Galleria mellonella, in vitro-in vivo correlation, invasive candidiasis, candidemia, echinocandins, triazoles
- MeSH terms
- Amphotericin B, Antifungal Agents, Azoles, Fungal Proteins, Drug Resistance, Fungal, Candida tropicalis
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