Murine model of antibiotic-associated Staphylococcus aureus gastrointestinal infections (SAGII) and colonization

Staphylococcus aureus is an opportunistic pathogen that can both colonize the gastrointestinal tract and cause antibiotic associated diarrhea.

To develop a robust murine model for S. aureus gastrointestinal infection (SAGII) and colonization, mice were (a) treated with varying antibiotic regimes prior to infection, (b) infected with either a methicillin-sensitive S. aureus (MSSA) or a methicillin-resistant S. aureus (MRSA) strain, (c) challenged with different bacterial inocula (d) tested for sexual dimorphism of SAGII virulence, and (e) tested for macronutrient effects on SAGII onset and virulence.

Antibiotic-treated male mice (but not female mice) were highly susceptible to both an MSSA and an MRSA strains. Interestingly, male mice challenged with the laboratory MSSA strain showed more severe and more prolonged SAGII symptomatology than animals challenged with the clinical MRSA strain. Diet composition significantly influenced disease outcome: a high-carbohydrate diet and a high-fat diet led to asymptomatic intestinal colonization followed by delayed SAGII sign onset in male mice. In contrast, a high-protein diet led to an early onset of SAGII signs followed by severe SAGII signs two weeks post-challenge. Furthermore, only the high-protein diet sensitized female mice to SAGII, but their symptomatology remained less severe than in male mice.

We developed a robust murine model for antibiotic-associated S. aureus gastrointestinal infection and colonization. This model shows both sexual dimorphism and macronutrient preference for SAGII signs severity. Diet manipulation can also be used to establish S. aureus colonization of the GI tract. Furthermore, the SAGII murine model demonstrates essential features of S. aureus pathogenesis which could provide understanding about human gastrointestinal colonization and infection mechanisms.