Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

Daniela Mailaender-Sanchez; Christina Braunsdorf; Christian Grumaz; Christoph Mueller; Stefan Lorenz; Philip Stevens; Jeanette Wagener; Betty Hebecker; Bernhard Hube; Franz Bracher; Kai Sohn; Martin Schaller

doi:10.1371/journal.pone.0184438

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

Daniela Mailaender-Sanchez, Christina Braunsdorf, Christian Grumaz, Christoph Mueller, Stefan Lorenz, Philip Stevens, Jeanette Wagener, Betty Hebecker, Bernhard Hube, Franz Bracher, Kai Sohn, Martin Schaller^*

^*Corresponding author for this work

Medical Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

Original language	English
Article number	0184438
Number of pages	19
Journal	PloS ONE
Volume	12
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0184438
Publication status	Published - 12 Oct 2017

Bibliographical note

Data Availability: All relevant data are available from the Gene Expression Omnibus at the following accession number: GSE97755.

Funding: This work was funded by the German Research Council (DFG) Graduation College 685, Dr. Jekyll and Mr. Hyde: A systems approach to the therapy of nosocomial infections caused by Candida albicans: a commensal organism switches to a deadly pathogen/ PTJ (FKZ: 0315409BBMBF), the Dr. Manfred Plempel-foundation, the Dr. Siegried Stettendorf-Foundation, the InfectERA Program (FunComPath; BMBF FKZ 031L0001A), the Integrated Research and Treatment Center for Sepsis Control and Care (CSCC) project CanBac (BMBF, FKZ: 01EO1002), and the German Research Council (DFG) GZ:HE7565/1-1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords

VULVO-VAGINAL CANDIDIASIS
IRRITABLE-BOWEL-SYNDROME
FUNGAL-INFECTIONS
RANDOMIZED-TRIAL
GENE-EXPRESSION
FATTY-ACID
ALBICANS
DIARRHEA
ASSAY
SUPPLEMENTATION

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1371/journal.pone.0184438Licence: CC BY

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion
Copyright: © 2017 Mailänder-Sánchez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. https://creativecommons.org/licenses/by/4.0/
Final published version, 5.41 MBLicence: CC BY

Cite this

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title = "Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion",

abstract = "Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.",

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author = "Daniela Mailaender-Sanchez and Christina Braunsdorf and Christian Grumaz and Christoph Mueller and Stefan Lorenz and Philip Stevens and Jeanette Wagener and Betty Hebecker and Bernhard Hube and Franz Bracher and Kai Sohn and Martin Schaller",

note = "Data Availability: All relevant data are available from the Gene Expression Omnibus at the following accession number: GSE97755. Funding: This work was funded by the German Research Council (DFG) Graduation College 685, Dr. Jekyll and Mr. Hyde: A systems approach to the therapy of nosocomial infections caused by Candida albicans: a commensal organism switches to a deadly pathogen/ PTJ (FKZ: 0315409BBMBF), the Dr. Manfred Plempel-foundation, the Dr. Siegried Stettendorf-Foundation, the InfectERA Program (FunComPath; BMBF FKZ 031L0001A), the Integrated Research and Treatment Center for Sepsis Control and Care (CSCC) project CanBac (BMBF, FKZ: 01EO1002), and the German Research Council (DFG) GZ:HE7565/1-1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.",

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T1 - Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

AU - Mailaender-Sanchez, Daniela

AU - Braunsdorf, Christina

AU - Grumaz, Christian

AU - Mueller, Christoph

AU - Lorenz, Stefan

AU - Stevens, Philip

AU - Wagener, Jeanette

AU - Hebecker, Betty

AU - Hube, Bernhard

AU - Bracher, Franz

AU - Sohn, Kai

AU - Schaller, Martin

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N2 - Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

AB - Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnosus GG (LGG) in prevention of mucosal C. albicans infections. Here, we demonstrate that LGG protects oral epithelial tissue from damage caused by C. albicans in our in vitro model of oral candidiasis. Furthermore, we provide insights into the mechanisms behind this protection and dissect direct and indirect effects of LGG on C. albicans pathogenicity. C. albicans viability was not affected by LGG. Instead, transcriptional profiling using RNA-Seq indicated dramatic metabolic reprogramming of C. albicans. Additionally, LGG had a significant impact on major virulence attributes, including adhesion, invasion, and hyphal extension, whose reduction, consequently, prevented epithelial damage. This was accompanied by glucose depletion and repression of ergosterol synthesis, caused by LGG, but also due to blocked adhesion sites. Therefore, LGG protects oral epithelia against C. albicans infection by preventing fungal adhesion, invasion and damage, driven, at least in parts, by metabolic reprogramming due to nutrient limitation caused by LGG.

KW - VULVO-VAGINAL CANDIDIASIS

KW - IRRITABLE-BOWEL-SYNDROME

KW - FUNGAL-INFECTIONS

KW - RANDOMIZED-TRIAL

KW - GENE-EXPRESSION

KW - FATTY-ACID

KW - ALBICANS

KW - DIARRHEA

KW - ASSAY

KW - SUPPLEMENTATION

U2 - 10.1371/journal.pone.0184438

DO - 10.1371/journal.pone.0184438

M3 - Article

SN - 1932-6203

VL - 12

JO - PloS ONE

JF - PloS ONE

IS - 10

M1 - 0184438

ER -

Antifungal defense of probiotic Lactobacillus rhamnosus GG is mediated by blocking adhesion and nutrient depletion

Abstract

Bibliographical note

Keywords

UN SDGs

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