Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection

ABSTRACT One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune sy...

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Autores principales:	Casandra L. Hoffman, Jonathan Lalsiamthara, Alejandro Aballay
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Caenorhabditis elegans Pseudomonas aeruginosa bacterial colonization host-pathogen interactions infection innate immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c8620739a0534d7c894b6ee927642b5c
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spelling	oai:doaj.org-article:c8620739a0534d7c894b6ee927642b5c2021-11-15T15:57:03ZHost Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection10.1128/mBio.00060-202150-7511https://doaj.org/article/c8620739a0534d7c894b6ee927642b5c2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00060-20https://doaj.org/toc/2150-7511ABSTRACT One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Pseudomonas aeruginosa. Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by P. aeruginosa to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides N-acetyl-galactosamine and N-acetylglucosamine are required for P. aeruginosa killing of Caenorhabditis elegans. We also found that the defective adhesion of P. aeruginosa to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in C. elegans lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as P. aeruginosa that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides. IMPORTANCE One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of Pseudomonas aeruginosa to colonize the intestine and ultimately cause death in Caenorhabditis elegans. We also demonstrate that monosaccharides alter the ability of bacteria to bind to both Caenorhabditis elegans intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.Casandra L. HoffmanJonathan LalsiamtharaAlejandro AballayAmerican Society for MicrobiologyarticleCaenorhabditis elegansPseudomonas aeruginosabacterial colonizationhost-pathogen interactionsinfectioninnate immunityMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Caenorhabditis elegans Pseudomonas aeruginosa bacterial colonization host-pathogen interactions infection innate immunity Microbiology QR1-502
spellingShingle	Caenorhabditis elegans Pseudomonas aeruginosa bacterial colonization host-pathogen interactions infection innate immunity Microbiology QR1-502 Casandra L. Hoffman Jonathan Lalsiamthara Alejandro Aballay Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection
description	ABSTRACT One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Pseudomonas aeruginosa. Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by P. aeruginosa to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides N-acetyl-galactosamine and N-acetylglucosamine are required for P. aeruginosa killing of Caenorhabditis elegans. We also found that the defective adhesion of P. aeruginosa to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in C. elegans lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as P. aeruginosa that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides. IMPORTANCE One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of Pseudomonas aeruginosa to colonize the intestine and ultimately cause death in Caenorhabditis elegans. We also demonstrate that monosaccharides alter the ability of bacteria to bind to both Caenorhabditis elegans intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.
format	article
author	Casandra L. Hoffman Jonathan Lalsiamthara Alejandro Aballay
author_facet	Casandra L. Hoffman Jonathan Lalsiamthara Alejandro Aballay
author_sort	Casandra L. Hoffman
title	Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection
title_short	Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection
title_full	Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection
title_fullStr	Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection
title_full_unstemmed	Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection
title_sort	host mucin is exploited by <named-content content-type="genus-species">pseudomonas aeruginosa</named-content> to provide monosaccharides required for a successful infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/c8620739a0534d7c894b6ee927642b5c
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Host Mucin Is Exploited by <named-content content-type="genus-species">Pseudomonas aeruginosa</named-content> To Provide Monosaccharides Required for a Successful Infection

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