Development of persistent gastrointestinal S. aureus carriage in mice

Abstract

One fifth to one quarter of the human population is asymptomatically, naturally and persistently colonised by Staphylococcus aureus. Observational human studies indicate that although the whole population is intermittently exposed, some individuals lose S. aureus rapidly. Others become persistent carriers, as assessed by nasal cultures, with many individuals colonised for decades. Current animal models of S. aureus colonisation are expensive and normally require antibiotics. Importantly, these animal models have not yet contributed to our poor understanding of the dichotomy in human colonisation status. Here, we identify a single strain of S. aureus found to be persistently colonising the gastrointestinal tract of BALB/c mice. Phylogenetic analyses suggest it diverged from a human ST15 lineage in the recent past. We show that murine carriage of this organism occurs in the bowel and nares, is acquired early in life, and can persist for months. Importantly, we observe the development of persistent and non-persistent gastrointestinal carriage states in genetically identical mice. We developed a needle- and antibiotic-free model in which we readily induced S. aureus colonisation of the gastrointestinal tract experimentally by environmental exposure. Using our experimental model, impact of adaptive immunity on S. aureus colonisation could be assessed. Vaccine efficacy to eliminate colonisation could also be investigated using this model.

Staphylococcus aureus Vaccine Research and Development: The Past, Present and Future, Including Novel Therapeutic Strategies

“…An additional caution to be noted when using mouse models for the study of S. aureus pathology is that specific pathogen free mice purchased from commercial vendors, as well as laboratory housed mice, may be naturally colonized with mouse-adapted S. aureus ( 109 – 111 ). Considering that pre-exposure to S. aureus in the contexts of colonization and infection alter the host immune response to subsequent infection, as reported in both mice and humans ( 112 – 114 ), the potentiality that experimental mice may or not be pre-colonized introduces a confounding factor into preclinical research.…”

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

“…Moreover, a CC15 isolate (SaF_1) originating from a colony of BALB/c mice also persistently colonized the gastrointestinal tract of BALB/c mice after environmental exposure. Interestingly, the authors observed the development of persistent and intermittent gastrointestinal carriage states in genetically identical mice, which points to the microbiome as a decisive factor in this setting [ 173 ].…”

Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent

“…In general, males are more susceptible to gastrointestinal and respiratory infections, whereas females are more affected by autoimmune diseases in part due to the pro-inflammatory effect of estradiol, but these responses are tissue and cell specific 17,19 . In the few studies examining GI MRSA colonization in mice, the focus has been on the adaptation of S. aureus to the host [24][25][26][27] .…”