1. Asymptomatic carriage of group A streptococcus is associated with elimination of capsule production.
- Author
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Flores AR, Jewell BE, Olsen RJ, Shelburne SA 3rd, Fittipaldi N, Beres SB, and Musser JM
- Subjects
- Animals, Bacterial Capsules genetics, Bacterial Proteins genetics, Bacterial Proteins metabolism, Cell Line, Epithelial Cells metabolism, Epithelial Cells microbiology, Female, Humans, Hyaluronic Acid genetics, Hyaluronic Acid metabolism, Mice, Mutation genetics, Operon genetics, Oropharynx metabolism, Oropharynx microbiology, Streptococcal Infections genetics, Streptococcal Infections microbiology, Streptococcus genetics, Virulence Factors genetics, Virulence Factors metabolism, Bacterial Capsules metabolism, Streptococcal Infections metabolism, Streptococcus metabolism
- Abstract
Humans commonly carry pathogenic bacteria asymptomatically, but despite decades of study, the underlying molecular contributors remain poorly understood. Here, we show that a group A streptococcus carriage strain contains a frameshift mutation in the hasA gene resulting in loss of hyaluronic acid capsule biosynthesis. This mutation was repaired by allelic replacement, resulting in restoration of capsule production in the isogenic derivative strain. The "repaired" isogenic strain was significantly more virulent than the carriage strain in a mouse model of necrotizing fasciitis and had enhanced growth ex vivo in human blood. Importantly, the repaired isogenic strain colonized the mouse oropharynx with significantly greater bacterial burden and had significantly reduced ability to internalize into cultured epithelial cells than the acapsular carriage strain. We conducted full-genome sequencing of 81 strains cultured serially from 19 epidemiologically unrelated human subjects and discovered the common theme that mutations negatively affecting capsule biosynthesis arise in vivo in the has operon. The significantly decreased capsule production is a key factor contributing to the molecular détente between pathogen and host. Our discoveries suggest a general model for bacterial pathogens in which mutations that downregulate or ablate virulence factor production contribute to carriage., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Published
- 2014
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