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Bacillus subtilis engineered for topical delivery of an antifungal agent

Fungal skin infections are a common condition affecting 20–25 percent of the world population. While these conditions are treatable with regular application of an antifungal medication, we sought to develop a more convenient, longer-lasting topical antifungal platform that could increase patient adh...

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Autores principales: Montgomery, Veronica A., Cain, Ethan, Styczynski, Mark P., Prausnitz, Mark R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688720/
https://www.ncbi.nlm.nih.gov/pubmed/38032939
http://dx.doi.org/10.1371/journal.pone.0293664
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author Montgomery, Veronica A.
Cain, Ethan
Styczynski, Mark P.
Prausnitz, Mark R.
author_facet Montgomery, Veronica A.
Cain, Ethan
Styczynski, Mark P.
Prausnitz, Mark R.
author_sort Montgomery, Veronica A.
collection PubMed
description Fungal skin infections are a common condition affecting 20–25 percent of the world population. While these conditions are treatable with regular application of an antifungal medication, we sought to develop a more convenient, longer-lasting topical antifungal platform that could increase patient adherence to treatment regimens by using Bacillus subtilis, a naturally antifungal bacteria found on the skin, for drug production and delivery. In this study, we engineered B. subtilis for increased production of the antifungal lipopeptide iturin A by overexpression of the pleiotropic regulator DegQ. The engineered strain had an over 200% increase in iturin A production as detected by HPLC, accompanied by slower growth but the same terminal cell density as determined by absorbance measurements of liquid culture. In an in vitro antifungal assay, we found that despite its higher iturin A production, the engineered strain was less effective at reducing the growth of a plug of the pathogenic fungus Trichophyton mentagrophytes on an agar plate compared to the parent strain. The reduced efficacy of the engineered strain may be explained by its reduced growth rate, which highlights the need to address trade-offs between titers (e.g. measured drug production) and other figures of merit (e.g. growth rate) during metabolic engineering.
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spelling pubmed-106887202023-12-01 Bacillus subtilis engineered for topical delivery of an antifungal agent Montgomery, Veronica A. Cain, Ethan Styczynski, Mark P. Prausnitz, Mark R. PLoS One Research Article Fungal skin infections are a common condition affecting 20–25 percent of the world population. While these conditions are treatable with regular application of an antifungal medication, we sought to develop a more convenient, longer-lasting topical antifungal platform that could increase patient adherence to treatment regimens by using Bacillus subtilis, a naturally antifungal bacteria found on the skin, for drug production and delivery. In this study, we engineered B. subtilis for increased production of the antifungal lipopeptide iturin A by overexpression of the pleiotropic regulator DegQ. The engineered strain had an over 200% increase in iturin A production as detected by HPLC, accompanied by slower growth but the same terminal cell density as determined by absorbance measurements of liquid culture. In an in vitro antifungal assay, we found that despite its higher iturin A production, the engineered strain was less effective at reducing the growth of a plug of the pathogenic fungus Trichophyton mentagrophytes on an agar plate compared to the parent strain. The reduced efficacy of the engineered strain may be explained by its reduced growth rate, which highlights the need to address trade-offs between titers (e.g. measured drug production) and other figures of merit (e.g. growth rate) during metabolic engineering. Public Library of Science 2023-11-30 /pmc/articles/PMC10688720/ /pubmed/38032939 http://dx.doi.org/10.1371/journal.pone.0293664 Text en © 2023 Montgomery et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Montgomery, Veronica A.
Cain, Ethan
Styczynski, Mark P.
Prausnitz, Mark R.
Bacillus subtilis engineered for topical delivery of an antifungal agent
title Bacillus subtilis engineered for topical delivery of an antifungal agent
title_full Bacillus subtilis engineered for topical delivery of an antifungal agent
title_fullStr Bacillus subtilis engineered for topical delivery of an antifungal agent
title_full_unstemmed Bacillus subtilis engineered for topical delivery of an antifungal agent
title_short Bacillus subtilis engineered for topical delivery of an antifungal agent
title_sort bacillus subtilis engineered for topical delivery of an antifungal agent
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688720/
https://www.ncbi.nlm.nih.gov/pubmed/38032939
http://dx.doi.org/10.1371/journal.pone.0293664
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