Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35

Abstract GYNOPHILUS (Lcr REGENERANS) is a live biotherapeutic product (LBP) aimed at restoring the vaginal microbiome and contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35. In this study, the LBP formulation and manufacturing process significantly enhanced the anti-Candida...

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Main Authors: Caroline Dausset, Stéphanie Bornes, Sylvie Miquel, Nathalie Kondjoyan, Magaly Angenieux, Laurence Nakusi, Philippe Veisseire, Elina Alaterre, Luis G. Bermúdez-Humarán, Philippe Langella, Erwan Engel, Christiane Forestier, Adrien Nivoliez
Format: Article
Language:English
Published: Nature Portfolio 2020-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-74027-7
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author Caroline Dausset
Stéphanie Bornes
Sylvie Miquel
Nathalie Kondjoyan
Magaly Angenieux
Laurence Nakusi
Philippe Veisseire
Elina Alaterre
Luis G. Bermúdez-Humarán
Philippe Langella
Erwan Engel
Christiane Forestier
Adrien Nivoliez
author_facet Caroline Dausset
Stéphanie Bornes
Sylvie Miquel
Nathalie Kondjoyan
Magaly Angenieux
Laurence Nakusi
Philippe Veisseire
Elina Alaterre
Luis G. Bermúdez-Humarán
Philippe Langella
Erwan Engel
Christiane Forestier
Adrien Nivoliez
author_sort Caroline Dausset
collection DOAJ
description Abstract GYNOPHILUS (Lcr REGENERANS) is a live biotherapeutic product (LBP) aimed at restoring the vaginal microbiome and contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35. In this study, the LBP formulation and manufacturing process significantly enhanced the anti-Candida activity of L. rhamnosus Lcr35, with a complete loss of viability of the yeast after 48 h of coincubation. Sodium thiosulfate (STS), one excipient of the product, was used as a potentiator of the anti-Candida spp. activity of Lactobacilli. This contact-independent phenomenon induced fungal cell disturbances, as observed by electron microscopy observations. Nonverbal sensory experiments showed clear odor dissimilarities between cocultures of L. rhamnosus Lcr35 and C. albicans in the presence and absence of STS, suggesting an impact of odor-active metabolites. A volatolomic approach allowed the identification of six odor-active compounds, including one sulfur compound that was identified as S-methyl thioacetate (MTA). MTA was associated with the antifungal effect of Lcr35, and its functional link was established in vitro. We show for the first time that the LBP GYNOPHILUS, which is a highly active product in the reduction of vulvovaginal candidiasis, requires the presence of a sulfur compound to fully achieve its antifungal effect.
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spelling doaj.art-64762751c0964b09911a1fa99fa13b362022-12-21T23:33:40ZengNature PortfolioScientific Reports2045-23222020-10-0110111210.1038/s41598-020-74027-7Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35Caroline Dausset0Stéphanie Bornes1Sylvie Miquel2Nathalie Kondjoyan3Magaly Angenieux4Laurence Nakusi5Philippe Veisseire6Elina Alaterre7Luis G. Bermúdez-Humarán8Philippe Langella9Erwan Engel10Christiane Forestier11Adrien Nivoliez12Research and Development Department, BIOSEUniversité Clermont Auvergne, INRAE, VetAgro Sup, UMRFUniversité Clermont Auvergne, CNRS, Laboratoire Microorganismes : Génome et EnvironnementINRAE, UR370 QuaPA, Microcontaminants, Aroma & Separation Science Group (MASS)INRAE, UR370 QuaPA, Microcontaminants, Aroma & Separation Science Group (MASS)Université Clermont Auvergne, CNRS, Laboratoire Microorganismes : Génome et EnvironnementUniversité Clermont Auvergne, INRAE, VetAgro Sup, UMRFResearch and Development Department, BIOSEMicalis Institute, INRAE, AgroParisTech, Université Paris-SaclayMicalis Institute, INRAE, AgroParisTech, Université Paris-SaclayINRAE, UR370 QuaPA, Microcontaminants, Aroma & Separation Science Group (MASS)Université Clermont Auvergne, CNRS, Laboratoire Microorganismes : Génome et EnvironnementResearch and Development Department, BIOSEAbstract GYNOPHILUS (Lcr REGENERANS) is a live biotherapeutic product (LBP) aimed at restoring the vaginal microbiome and contains the live biotherapeutic microorganism Lactobacillus rhamnosus Lcr35. In this study, the LBP formulation and manufacturing process significantly enhanced the anti-Candida activity of L. rhamnosus Lcr35, with a complete loss of viability of the yeast after 48 h of coincubation. Sodium thiosulfate (STS), one excipient of the product, was used as a potentiator of the anti-Candida spp. activity of Lactobacilli. This contact-independent phenomenon induced fungal cell disturbances, as observed by electron microscopy observations. Nonverbal sensory experiments showed clear odor dissimilarities between cocultures of L. rhamnosus Lcr35 and C. albicans in the presence and absence of STS, suggesting an impact of odor-active metabolites. A volatolomic approach allowed the identification of six odor-active compounds, including one sulfur compound that was identified as S-methyl thioacetate (MTA). MTA was associated with the antifungal effect of Lcr35, and its functional link was established in vitro. We show for the first time that the LBP GYNOPHILUS, which is a highly active product in the reduction of vulvovaginal candidiasis, requires the presence of a sulfur compound to fully achieve its antifungal effect.https://doi.org/10.1038/s41598-020-74027-7
spellingShingle Caroline Dausset
Stéphanie Bornes
Sylvie Miquel
Nathalie Kondjoyan
Magaly Angenieux
Laurence Nakusi
Philippe Veisseire
Elina Alaterre
Luis G. Bermúdez-Humarán
Philippe Langella
Erwan Engel
Christiane Forestier
Adrien Nivoliez
Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35
Scientific Reports
title Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35
title_full Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35
title_fullStr Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35
title_full_unstemmed Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35
title_short Identification of sulfur components enhancing the anti-Candida effect of Lactobacillus rhamnosus Lcr35
title_sort identification of sulfur components enhancing the anti candida effect of lactobacillus rhamnosus lcr35
url https://doi.org/10.1038/s41598-020-74027-7
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