Abstract
More effective antibiotics and a protective vaccine are desperately needed to combat the ‘superbug’ Staphylococcus aureus. While in vivo pathogenicity studies routinely involve infection of mice with human S. aureus isolates, recent genetic studies have demonstrated that S. aureus lineages are largely host-specific. The use of such animal-adapted S. aureus strains may therefore be a promising approach for developing more clinically relevant animal infection models. We have isolated a mouse-adapted S. aureus strain (JSNZ) which caused a severe outbreak of preputial gland abscesses among male C57BL/6J mice. We aimed to extensively characterize this strain on a genomic level and determine its virulence potential in murine colonization and infection models. JSNZ belongs to the MLST type ST88, rare among human isolates, and lacks an hlb-converting phage encoding human-specific immune evasion factors. Naive mice were found to be more susceptible to nasal and gastrointestinal colonization with JSNZ than with the human-derived Newman strain. Furthermore, naïve mice required antibiotic pre-treatment to become colonized with Newman. In contrast, JSNZ was able to colonize mice in the absence of antibiotic treatment suggesting that this strain can compete with the natural flora for space and nutrients. In a renal abscess model, JSNZ caused more severe disease than Newman with greater weight loss and bacterial burden. In contrast to most other clinical isolates, JSNZ can also be readily genetically modified by phage transduction and electroporation. In conclusion, the mouse-adapted strain JSNZ may represent a valuable tool for studying aspects of mucosal colonization and for screening novel vaccines and therapies directed at preventing colonization.
Highlights
The high incidence of illness and death within hospitals and the community caused by the bacterium Staphylococcus aureus, and the multidrug resistant nature of many isolates is reason for concern [1,2,3]
We propose that the use of animal-adapted S. aureus strains could be a promising approach for developing clinically relevant animal infection models, because such strains should show enhanced fitness in their natural hosts when compared to human-adapted isolates
We demonstrate that JSNZ belongs to the multilocus sequence typing (MLST) type ST88, which is rare among human isolates, and lacks the human-specific hlb-converting phage
Summary
The high incidence of illness and death within hospitals and the community caused by the bacterium Staphylococcus aureus, and the multidrug resistant nature of many isolates is reason for concern [1,2,3]. S. aureus is a frequent colonizer of the human mucosa and skin. It is well established that mucosal colonization with S. aureus is major risk factor for the development of disease and transmission of bacteria to susceptible individuals [6,8]. Nasal carriage can be transiently eradicated by topical administration of the antibiotic mupirocin but this is compromised by the development of resistance [9]. To develop alternative strategies for reducing nasal carriage, a detailed understanding of the molecular basis of interactions between the host and the bacterium that underlie the process is urgently required. There is a strong need for a robust and sustained mucosal colonization model that closely mimics the human clinical situation
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