Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria

Abstract The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat...

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Main Authors: Miroslav Dinić, Stefan Jakovljević, Jelena Đokić, Nikola Popović, Dušan Radojević, Ivana Strahinić, Nataša Golić
Format: Article
Language:English
Published: Nature Portfolio 2021-10-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-00698-5
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author Miroslav Dinić
Stefan Jakovljević
Jelena Đokić
Nikola Popović
Dušan Radojević
Ivana Strahinić
Nataša Golić
author_facet Miroslav Dinić
Stefan Jakovljević
Jelena Đokić
Nikola Popović
Dušan Radojević
Ivana Strahinić
Nataša Golić
author_sort Miroslav Dinić
collection DOAJ
description Abstract The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat-inactivated probiotic strain Lactobacillus curvatus BGMK2-41 stimulates immune response and resistance of the Caenorhabditis elegans against Staphylococcus aureus and Pseudomonas aeruginosa. By employing qRT-PCR and western blot analysis we showed that heat-inactivated BGMK2-41 activated PMK-1/p38 MAPK immunity pathway which prolongs the survival of C. elegans exposed to pathogenic bacteria in nematode killing assays. The C. elegans pmk-1 mutant was used to demonstrate a mechanistic basis for the antimicrobial potential of BGMK2-41, showing that BGMK2-41 upregulated PMK-1/p38 MAPK dependent transcription of C-type lectins, lysozymes and tight junction protein CLC-1. Overall, this study suggests that PMK-1/p38 MAPK‐dependent immune regulation by BGMK2-41 is essential for probiotic-mediated C. elegans protection against gram-positive and gram-negative bacteria and could be further explored for development of probiotics with the potential to increase resistance of the host towards pathogens.
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spelling doaj.art-cdc871a4ceb448c9a6d297cf0d52c4ff2022-12-21T21:47:19ZengNature PortfolioScientific Reports2045-23222021-10-0111111010.1038/s41598-021-00698-5Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteriaMiroslav Dinić0Stefan Jakovljević1Jelena Đokić2Nikola Popović3Dušan Radojević4Ivana Strahinić5Nataša Golić6Laboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of BelgradeLaboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of BelgradeLaboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of BelgradeLaboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of BelgradeLaboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of BelgradeLaboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of BelgradeLaboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of BelgradeAbstract The host-microbiota cross-talk represents an important factor contributing to innate immune response and host resistance during infection. It has been shown that probiotic lactobacilli exhibit the ability to modulate innate immunity and enhance pathogen elimination. Here we showed that heat-inactivated probiotic strain Lactobacillus curvatus BGMK2-41 stimulates immune response and resistance of the Caenorhabditis elegans against Staphylococcus aureus and Pseudomonas aeruginosa. By employing qRT-PCR and western blot analysis we showed that heat-inactivated BGMK2-41 activated PMK-1/p38 MAPK immunity pathway which prolongs the survival of C. elegans exposed to pathogenic bacteria in nematode killing assays. The C. elegans pmk-1 mutant was used to demonstrate a mechanistic basis for the antimicrobial potential of BGMK2-41, showing that BGMK2-41 upregulated PMK-1/p38 MAPK dependent transcription of C-type lectins, lysozymes and tight junction protein CLC-1. Overall, this study suggests that PMK-1/p38 MAPK‐dependent immune regulation by BGMK2-41 is essential for probiotic-mediated C. elegans protection against gram-positive and gram-negative bacteria and could be further explored for development of probiotics with the potential to increase resistance of the host towards pathogens.https://doi.org/10.1038/s41598-021-00698-5
spellingShingle Miroslav Dinić
Stefan Jakovljević
Jelena Đokić
Nikola Popović
Dušan Radojević
Ivana Strahinić
Nataša Golić
Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria
Scientific Reports
title Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria
title_full Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria
title_fullStr Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria
title_full_unstemmed Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria
title_short Probiotic-mediated p38 MAPK immune signaling prolongs the survival of Caenorhabditis elegans exposed to pathogenic bacteria
title_sort probiotic mediated p38 mapk immune signaling prolongs the survival of caenorhabditis elegans exposed to pathogenic bacteria
url https://doi.org/10.1038/s41598-021-00698-5
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