Characterization of a Mouse-Adapted Staphylococcus aureus Strain

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.

Exogenous fatty acid metabolism in bacteria

“…It is plausible that endogenous fatty acid synthesis is not required in the bacteremia model, but is required for the peritonitis model. It is also important to note that S. aureus lineages are largely host species specific, and mice are not natural hosts for many of the S. aureus strains derived from human infections [88]. Because there is no gold standard mouse model for mimicking Staphylococcus infection in humans, the FabD mutant should be tested in other models simulating other phases of infection beyond blood growth to determine if FASII inhibitors are effective therapeutics.…”

Animal models of hospital-acquired pneumonia: current practices and future perspectives

“…An important issue that also needs to be addressed is the fact that different bacterial strains are host-specific (82) and only express certain virulence factors depending on the particular host niche (83). In that respect, clinical isolates might not be ideally suited to establish pneumonia in a rodent model, but, on the other hand, rodent adapted bacterial strains might lack expression of specific key virulence factors and thus provoke an altered immune response (84,85).…”

Mouse models for infectious diseases caused by Staphylococcus aureus

“…Mice are, however, not a natural host for human clinical S. aureus isolates and require genetic adaptation to cause transmissible disease in mouse facilities (38). Key clinical presentation of natural S. aureus infection is the development of preputial gland abscess lesions in male mice as well as nasal and gastrointestinal colonization (38).…”

“…Key clinical presentation of natural S. aureus infection is the development of preputial gland abscess lesions in male mice as well as nasal and gastrointestinal colonization (38). Because most experimental approaches are designed towards elucidating the virulence factors of human clinical isolates and deriving protective vaccines for humans, mouse isolates have not yet been examined in detail.…”