The objective of this study was to investigate the in vivo activity of the lantibiotic lacticin 3147 against the luminescent Staphylococcus aureus strain Xen 29 using a murine model. Female BALB/c mice (7 weeks old, 17g) were divided into groups (n = 5) and infected with the Xen 29 strain via the intraperitoneal route at a dose of 1 10 6 cfu/animal. After 1.5hr, the animals were treated subcutaneously with doses of phosphate-buffered saline (PBS; negative control) or lacticin 3147. Luminescent imaging was carried 3 and 5 hours postinfection. Mice were then sacrificed, and the levels of S. aureus Xen 29 in the liver, spleen, and kidneys were quantified. Notably, photoluminescence and culture-based analysis both revealed that lacticin 3147 successfully controlled the systemic spread of S. aureus in mice thus indicating that lacticin 3147 has potential as a chemotherapeutic agent for in vivo applications. © 2012 Clare Piper et al.