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Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16.

ABSTRACT: The distal colon functions as a bioreactor and harbors an enormous amount of bacteria in a mutualistic relationship with the host. The microbiota have to be kept at a safe distance to prevent inflammation, something that is achieved by a dense inner mucus layer that lines the epithelial cells. The large polymeric nets made up by the heavily O-glycosylated MUC2 mucin forms this physical barrier. Proteomic analyses of mucus have identified the lectin-like protein ZG16 (zymogen granulae protein 16) as an abundant mucus component. To elucidate the function of ZG16, we generated recombinant ZG16 and studied Zg16-/- mice. ZG16 bound to and aggregated Gram-positive bacteria via binding to the bacterial cell wall peptidoglycan. Zg16-/- mice have a distal colon mucus layer with normal thickness, but with bacteria closer to the epithelium. Using distal colon explants mounted in a horizontal perfusion chamber we demonstrated that treatment of bacteria with recombinant ZG16 hindered bacterial penetration into the mucus. The inner colon mucus of Zg16-/- animals had a higher load of Gram-positive bacteria and showed bacteria with higher motility in the mucus close to the host epithelium compared with cohoused littermate Zg16+/+ The more penetrable Zg16-/- mucus allowed Gram-positive bacteria to translocate to systemic tissues. Viable bacteria were found in spleen and were associated with increased abdominal fat pad mass in Zg16-/- animals. The function of ZG16 reveals a mechanism for keeping bacteria further away from the host colon epithelium.

SUBMITTER: Bergstrom JH

PROVIDER: S-EPMC5137749 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16.

Bergström Joakim H JH Birchenough George M H GM Katona Gergely G Schroeder Bjoern O BO Schütte André A Ermund Anna A Johansson Malin E V ME Hansson Gunnar C GC

Proceedings of the National Academy of Sciences of the United States of America 20161114 48

The distal colon functions as a bioreactor and harbors an enormous amount of bacteria in a mutualistic relationship with the host. The microbiota have to be kept at a safe distance to prevent inflammation, something that is achieved by a dense inner mucus layer that lines the epithelial cells. The large polymeric nets made up by the heavily O-glycosylated MUC2 mucin forms this physical barrier. Proteomic analyses of mucus have identified the lectin-like protein ZG16 (zymogen granulae protein 16) ...[more]

PMID: 27849619

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Project description:Low molecular weight (LMW) thiols play an important role as thiol-cofactors for many enzymes and are crucial to maintain the reduced state of the cytoplasm. Most Gram-negative bacteria utilize glutathione (GSH) as major LMW thiol. However, in Gram-positive Actinomycetes and Firmicutes alternative LMW thiols, such as mycothiol (MSH) and bacillithiol (BSH) play related roles as GSH surrogates, respectively. Under conditions of hypochlorite stress, MSH and BSH are known to form mixed disulfides with protein thiols, termed as S-mycothiolation or S-bacillithiolation that function in thiol-protection and redox regulation. Protein S-thiolations are widespread redox-modifications discovered in different Gram-positive bacteria, such as Bacillus and Staphylococcus species, Mycobacterium smegmatis, Corynebacterium glutamicum and Corynebacterium diphtheriae. S-thiolated proteins are mainly involved in cellular metabolism, protein translation, redox regulation and antioxidant functions with some conserved targets across bacteria. The reduction of protein S-mycothiolations and S-bacillithiolations requires glutaredoxin-related mycoredoxin and bacilliredoxin pathways to regenerate protein functions. In this review, we present an overview of the functions of mycothiol and bacillithiol and their physiological roles in protein S-bacillithiolations and S-mycothiolations in Gram-positive bacteria. Significant progress has been made to characterize the role of protein S-thiolation in redox-regulation and thiol protection of main metabolic and antioxidant enzymes. However, the physiological roles of the pathways for regeneration are only beginning to emerge as well as their interactions with other cellular redox systems. Future studies should be also directed to explore the roles of protein S-thiolations and their redox pathways in pathogenic bacteria under infection conditions to discover new drug targets and treatment options against multiple antibiotic resistant bacteria.

Dataset Information

Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16.

Publications

Gram-positive bacteria are held at a distance in the colon mucus by the lectin-like protein ZG16.

Similar Datasets

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