Biological roles of the O-methyl phosphoramidate capsule modification in Campylobacter jejuni

Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, and the capsular polysaccharide (CPS) of this organism is required for persistence and disease. C. jejuni produces over 47 different capsular structures, including a unique O-methyl phosphoramidate (MeOPN) modification pre...

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Bibliographic Details
Published in:PloS one 2014-01, Vol.9 (1), p.e87051
Main Authors: van Alphen, Lieke B, Wenzel, Cory Q, Richards, Michele R, Fodor, Christopher, Ashmus, Roger A, Stahl, Martin, Karlyshev, Andrey V, Wren, Brendan W, Stintzi, Alain, Miller, William G, Lowary, Todd L, Szymanski, Christine M
Format: Article
Language:English
Subjects:
Agrochemicals
Amides - metabolism
Analysis
Animals
Bacteria
Bacterial Adhesion
Bacterial Capsules - enzymology
Bacterial Capsules - genetics
Bacterial Proteins - genetics
Biochemistry
Biology
Biosynthesis
Caco-2 Cells
Campylobacter
Campylobacter fetus
Campylobacter Infections - microbiology
Campylobacter jejuni
Campylobacter jejuni - enzymology
Campylobacter jejuni - genetics
Cell surface
Chemistry
Chickens
Colonization
Complement activation
Epithelial cells
Fetuses
Galleria mellonella
Gastroenteritis
Gene Knockout Techniques
Genes
Genomes
Genomics
Guillain-Barre syndrome
Humans
Immunology
Infections
Insecticide resistance
Insecticides - pharmacology
Insects
Larva - drug effects
Larva - microbiology
Larvae
Medicine
Microbial Viability
Monosaccharides
Moths - drug effects
Moths - microbiology
Mutants
NMR
Nuclear magnetic resonance
Pathogens
Pesticides
Phosphoric Acids - metabolism
Phylogeny
Polysaccharides
Polysaccharides, Bacterial - pharmacology
Polysaccharides, Bacterial - physiology
Poultry
Studies
Sus scrofa
Swine
Transferases - genetics
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Summary:Campylobacter jejuni is a major cause of bacterial gastroenteritis worldwide, and the capsular polysaccharide (CPS) of this organism is required for persistence and disease. C. jejuni produces over 47 different capsular structures, including a unique O-methyl phosphoramidate (MeOPN) modification present on most C. jejuni isolates. Although the MeOPN structure is rare in nature it has structural similarity to some synthetic pesticides. In this study, we have demonstrated, by whole genome comparisons and high resolution magic angle spinning NMR, that MeOPN modifications are common to several Campylobacter species. Using MeOPN biosynthesis and transferase mutants generated in C. jejuni strain 81-176, we observed that loss of MeOPN from the cell surface correlated with increased invasion of Caco-2 epithelial cells and reduced resistance to killing by human serum. In C. jejuni, the observed serum mediated killing was determined to result primarily from activation of the classical complement pathway. The C. jejuni MeOPN transferase mutant showed similar levels of colonization relative to the wild-type in chickens, but showed a five-fold drop in colonization when co-infected with the wild-type in piglets. In Galleria mellonella waxmoth larvae, the MeOPN transferase mutant was able to kill the insects at wild-type levels. Furthermore, injection of the larvae with MeOPN-linked monosaccharides or CPS purified from the wild-type strain did not result in larval killing, indicating that MeOPN does not have inherent insecticidal activity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0087051