Dataset Information

Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.

ABSTRACT: Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic colonization¹. In the oral cavity, saliva containing the mucins MUC5B and MUC7 forms a pellicle that coats the soft tissue and teeth to prevent infection by oral pathogens, such as Streptococcus mutans². Salivary mucin can interact directly with microorganisms through selective agglutinin activity and bacterial binding^2-4, but the extent and basis of the protective functions of saliva are not well understood. Here, using an ex vivo saliva model, we identify that MUC5B is an inhibitor of microbial virulence. Specifically, we find that natively purified MUC5B downregulates the expression of quorum-sensing pathways activated by the competence stimulating peptide and the sigX-inducing peptide⁵. Furthermore, MUC5B prevents the acquisition of antimicrobial resistance through natural genetic transformation, a process that is activated through quorum sensing. Our data reveal that the effect of MUC5B is mediated by its associated O-linked glycans, which are potent suppressors of quorum sensing and genetic transformation, even when removed from the mucin backbone. Together, these results present mucin O-glycans as a host strategy for domesticating potentially pathogenic microorganisms without killing them.

SUBMITTER: Werlang CA

PROVIDER: S-EPMC8811953 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.

Werlang Caroline A CA Chen Wesley G WG Aoki Kazuhiro K Wheeler Kelsey M KM Tymm Carly C Mileti Cassidy J CJ Burgos Ana C AC Kim Kris K Tiemeyer Michael M Ribbeck Katharina K

Nature microbiology 20210318 5

Mucus barriers accommodate trillions of microorganisms throughout the human body while preventing pathogenic colonization1. In the oral cavity, saliva containing the mucins MUC5B and MUC7 forms a pellicle that coats the soft tissue and teeth to prevent infection by oral pathogens, such as Streptococcus mutans2. Salivary mucin can interact directly with microorganisms through selective agglutinin activity and bacterial binding2-4, but the extent and basis of the p ...[more]

PMID: 33737747

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Project description:The genus Streptococcus encompasses a large bacterial taxon that commonly colonizes mucosal surfaces of vertebrates and is capable of disease etiologies originating from diverse body sites, including the respiratory, digestive, and reproductive tracts. Identifying new modes of treating infections is of increasing importance, as antibiotic resistance has escalated. Streptococcus mutans is an important opportunistic pathogen that is an agent of dental caries and is capable of systemic diseases such as endocarditis. As such, understanding how it regulates virulence and competes in the oral niche is a priority in developing strategies to defend from these pathogens. We determined that S. mutans UA159 possesses a bona fide short hydrophobic peptide (SHP)/Rgg quorum-sensing system that regulates a specialized biosynthetic operon featuring a radical-SAM (S-adenosyl-l-methionine) (RaS) enzyme and produces a ribosomally synthesized and posttranslationally modified peptide (RiPP). The pairing of SHP/Rgg regulatory systems with RaS biosynthetic operons is conserved across streptococci, and a locus similar to that in S. mutans is found in Streptococcus ferus, an oral streptococcus isolated from wild rats. We identified the RaS-RiPP product from this operon and solved its structure using a combination of analytical methods; we term these RiPPs tryglysin A and B for the unusual Trp-Gly-Lys linkage. We report that tryglysins specifically inhibit the growth of other streptococci, but not other Gram-positive bacteria such as Enterococcus faecalis or Lactococcus lactis We predict that tryglysin is produced by S. mutans in its oral niche, thus inhibiting the growth of competing species, including several medically relevant streptococci.IMPORTANCE Bacteria interact and compete with a large community of organisms in their natural environment. Streptococcus mutans is one such organism, and it is an important member of the oral microbiota. We found that S. mutans uses a quorum-sensing system to regulate production of a novel posttranslationally modified peptide capable of inhibiting growth of several streptococcal species. We find inhibitory properties of a similar peptide produced by S. ferus and predict that these peptides play a role in interspecies competition in the oral niche.

Dataset Information

Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.

Publications

Mucin O-glycans suppress quorum-sensing pathways and genetic transformation in Streptococcus mutans.

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