Staphylococcus aureus Colonization of the Mouse Gastrointestinal Tract Is Modulated by Wall Teichoic Acid, Capsule, and Surface Proteins.

Abstract

Staphylococcus aureus colonizes the nose, throat, skin, and gastrointestinal (GI) tract of humans. GI carriage of S. aureus is difficult to eradicate and has been shown to facilitate the transmission of the bacterium among individuals. Although staphylococcal colonization of the GI tract is asymptomatic, it increases the likelihood of infection, particularly skin and soft tissue infections caused by USA300 isolates. We established a mouse model of persistent S. aureus GI colonization and characterized the impact of selected surface antigens on colonization. In competition experiments, an acapsular mutant colonized better than the parental strain Newman, whereas mutants defective in sortase A and clumping factor A showed impaired ability to colonize the GI tract. Mutants lacking protein A, clumping factor B, poly-N-acetyl glucosamine, or SdrCDE showed no defect in colonization. An S. aureus wall teichoic acid (WTA) mutant (ΔtagO) failed to colonize the mouse nose or GI tract, and the tagO and clfA mutants showed reduced adherence in vitro to intestinal epithelial cells. The tagO mutant was recovered in lower numbers than the wild type strain in the murine stomach and duodenum 1 h after inoculation. This reduced fitness correlated with the in vitro susceptibility of the tagO mutant to bile salts, proteases, and a gut-associated defensin. Newman ΔtagO showed enhanced susceptibility to autolysis, and an autolysin (atl) tagO double mutant abrogated this phenotype. However, the atl tagO mutant did not survive better in the mouse GI tract than the tagO mutant. Our results indicate that the failure of the tagO mutant to colonize the GI tract correlates with its poor adherence and susceptibility to bactericidal factors within the mouse gut, but not to enhanced activity of its major autolysin.

• Authors: Yoshiki Misawa, Kathryn A Kelley, Xiaogang Wang, Linhui Wang, Wan Beom Park, Johannes Birtel, David Saslowsky, Jean C Lee
• Journal: PLoS pathogens (PLoS Pathog) Vol. 11 Issue 7 Pg. e1005061 (Jul 2015) ISSN: 1553-7374 [Electronic] United States
• PMID: 26201029 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Membrane Proteins
• Teichoic Acids
• N-Acetylmuramoyl-L-alanine Amidase

Topics

• Animals
• Anti-Bacterial Agents (metabolism, pharmacology)
• Bacterial Adhesion (drug effects)
• Bacterial Capsules (metabolism)
• Cell Wall (metabolism)
• Gastrointestinal Diseases (metabolism, microbiology)
• Humans
• Membrane Proteins (metabolism)
• Mice
• N-Acetylmuramoyl-L-alanine Amidase (metabolism)
• Staphylococcal Infections (microbiology)
• Staphylococcus aureus (drug effects, genetics)
• Teichoic Acids (metabolism)