Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a Systemic Immune Response—Note of Caution for In vivo Infection Experiments

Abstract

Whether mice are an appropriate model for <i>S. aureus</i> infection and vaccination studies is a matter of debate, because they are not considered as natural hosts of <i>S. aureus</i>. We previously identified a mouse-adapted <i>S. aureus</i> strain, which caused infections in laboratory mice. This raised the question whether laboratory mice are commonly colonized with <i>S. aureus</i> and whether this might impact on infection experiments. Publicly available health reports from commercial vendors revealed that <i>S. aureus</i> colonization is rather frequent, with rates as high as 21% among specific-pathogen-free mice. In animal facilities, <i>S. aureus</i> was readily transmitted from parents to offspring, which became persistently colonized. Among 99 murine <i>S. aureus</i> isolates from Charles River Laboratories half belonged to the lineage CC88 (54.5%), followed by CC15, CC5, CC188, and CC8. A comparison of human and murine <i>S. aureus</i> isolates revealed features of host adaptation. In detail, murine strains lacked <i>hlb</i>-converting phages and superantigen-encoding mobile genetic elements, and were frequently ampicillin-sensitive. Moreover, murine CC88 isolates coagulated mouse plasma faster than human CC88 isolates. Importantly, <i>S. aureus</i> colonization clearly primed the murine immune system, inducing a systemic IgG response specific for numerous <i>S. aureus</i> proteins, including several vaccine candidates. Phospholipase C emerged as a promising test antigen for monitoring <i>S. aureus</i> colonization in laboratory mice. In conclusion, laboratory mice are natural hosts of <i>S. aureus</i> and therefore, could provide better infection models than previously assumed. Pre-exposure to the bacteria is a possible confounder in <i>S. aureus</i> infection and vaccination studies and should be monitored.