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Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B

Cryptococcus neoformans is a leading cause of fungal meningitis in immunocompromized populations. Amphotericin B (AMB) and fluconazole (FLC) are common anticryptococcal agents. AMB treatment leads to severe side-effects. In contrast, FLC-based therapy is relatively safe, although C. neoformans often...

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Autores principales: Carlson, Tyler, Lupinacci, Emily, Moseley, Katie, Chandrasekaran, Srikripa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093136/
https://www.ncbi.nlm.nih.gov/pubmed/33877319
http://dx.doi.org/10.1093/femsle/fnab040
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author Carlson, Tyler
Lupinacci, Emily
Moseley, Katie
Chandrasekaran, Srikripa
author_facet Carlson, Tyler
Lupinacci, Emily
Moseley, Katie
Chandrasekaran, Srikripa
author_sort Carlson, Tyler
collection PubMed
description Cryptococcus neoformans is a leading cause of fungal meningitis in immunocompromized populations. Amphotericin B (AMB) and fluconazole (FLC) are common anticryptococcal agents. AMB treatment leads to severe side-effects. In contrast, FLC-based therapy is relatively safe, although C. neoformans often develops resistance to this drug. C. neoformans must adapt to the challenging environment of the human host. Environmental effects on potency of AMB and FLC and development of drug resistance remain poorly characterized. Here, the effects of nutrients, temperature and antioxidants on susceptibility of C. neoformans towards FLC and AMB were investigated. Limited nutrients led to a decrease and an increase of sensitivity towards FLC and AMB, respectively. Co-treatment with various antioxidants also demonstrated reciprocal effects on susceptibility towards FLC and AMB. In contrast, elevated temperature increased the efficacy of both drugs, although the effect on FLC was more drastic as compared to that of AMB. In addition, temperatures of 37°C and above prevented development of FLC resistance. Our study pointed to a critical role of the environment on susceptibility towards AMB and FLC and revealed reciprocal effects towards these antifungal drugs, reflecting contrasting modes of action of AMB and FLC.
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spelling pubmed-80931362021-05-10 Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B Carlson, Tyler Lupinacci, Emily Moseley, Katie Chandrasekaran, Srikripa FEMS Microbiol Lett Research Letter Cryptococcus neoformans is a leading cause of fungal meningitis in immunocompromized populations. Amphotericin B (AMB) and fluconazole (FLC) are common anticryptococcal agents. AMB treatment leads to severe side-effects. In contrast, FLC-based therapy is relatively safe, although C. neoformans often develops resistance to this drug. C. neoformans must adapt to the challenging environment of the human host. Environmental effects on potency of AMB and FLC and development of drug resistance remain poorly characterized. Here, the effects of nutrients, temperature and antioxidants on susceptibility of C. neoformans towards FLC and AMB were investigated. Limited nutrients led to a decrease and an increase of sensitivity towards FLC and AMB, respectively. Co-treatment with various antioxidants also demonstrated reciprocal effects on susceptibility towards FLC and AMB. In contrast, elevated temperature increased the efficacy of both drugs, although the effect on FLC was more drastic as compared to that of AMB. In addition, temperatures of 37°C and above prevented development of FLC resistance. Our study pointed to a critical role of the environment on susceptibility towards AMB and FLC and revealed reciprocal effects towards these antifungal drugs, reflecting contrasting modes of action of AMB and FLC. Oxford University Press 2021-04-20 /pmc/articles/PMC8093136/ /pubmed/33877319 http://dx.doi.org/10.1093/femsle/fnab040 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of FEMS. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Letter
Carlson, Tyler
Lupinacci, Emily
Moseley, Katie
Chandrasekaran, Srikripa
Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B
title Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B
title_full Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B
title_fullStr Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B
title_full_unstemmed Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B
title_short Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B
title_sort effects of environmental factors on sensitivity of cryptococcus neoformans to fluconazole and amphotericin b
topic Research Letter
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093136/
https://www.ncbi.nlm.nih.gov/pubmed/33877319
http://dx.doi.org/10.1093/femsle/fnab040
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