Influence of in vitro bacterial urokinase responsiveness on the in vivo pathogenesis of methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus in mouse models

Previous studies reported that clinical isolates of S. aureus may respond differently following addition of UK to in vitro growth medium, suggesting that the plasminogen activator influenced bacterial growth (Hart et al., 1996 and Hart and Woods, 1994). Two animal models were developed to further investigate these findings in an in vivo setting. CD1 mice and uPA-/- mice were intravenously inoculated with S. aureus and found to develop bacterial colonization primarily of the kidney and some joints. The uPA-/- mice were more susceptible to infection than the CD1 mice and also showed bacterial colonization of the heart. Preliminary investigations revealed that an inoculation dose of 107 CFU per mouse was optimal with regard to the development of chronic infection.; Using these two mouse models, UK responsive and UK non-responsive S. aureus isolates were tested for in vivo correspondence to in vitro findings. From the results, it appears that the in vitro UK phenotype does not overtly influence in vivo pathogenicity. When bacterial colonization of the kidney and mortality in vivo were assessed, UK responsive and UK non-responsive S. aureus isolates displayed similar results. The MSSA isolates tested did however show increased virulence compared to the MRSA isolates tested. This investigation also indicated that gender has an influence on bacterial colonization. Female mice were more susceptible to MRSA colonization and mortality than identically treated male mice, and castration of CD1 male mice resulted in an increase in bacterial colonization of the kidney, knee joint and elbow joint.