AUTHOR=Schulz Daniel , Grumann Dorothee , Trübe Patricia , Pritchett-Corning Kathleen , Johnson Sarah , Reppschläger Kevin , Gumz Janine , Sundaramoorthy Nandakumar , Michalik Stephan , Berg Sabine , van den Brandt Jens , Fister Richard , Monecke Stefan , Uy Benedict , Schmidt Frank , Bröker Barbara M. , Wiles Siouxsie , Holtfreter Silva 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=7

YEAR=2017

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2017.00152

DOI=10.3389/fcimb.2017.00152

ISSN=2235-2988

ABSTRACT=<p>Whether mice are an appropriate model for <italic>S. aureus</italic> infection and vaccination studies is a matter of debate, because they are not considered as natural hosts of <italic>S. aureus</italic>. We previously identified a mouse-adapted <italic>S. aureus</italic> strain, which caused infections in laboratory mice. This raised the question whether laboratory mice are commonly colonized with <italic>S. aureus</italic> and whether this might impact on infection experiments. Publicly available health reports from commercial vendors revealed that <italic>S. aureus</italic> colonization is rather frequent, with rates as high as 21% among specific-pathogen-free mice. In animal facilities, <italic>S. aureus</italic> was readily transmitted from parents to offspring, which became persistently colonized. Among 99 murine <italic>S. aureus</italic> 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 <italic>S. aureus</italic> isolates revealed features of host adaptation. In detail, murine strains lacked <italic>hlb</italic>-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, <italic>S. aureus</italic> colonization clearly primed the murine immune system, inducing a systemic IgG response specific for numerous <italic>S. aureus</italic> proteins, including several vaccine candidates. Phospholipase C emerged as a promising test antigen for monitoring <italic>S. aureus</italic> colonization in laboratory mice. In conclusion, laboratory mice are natural hosts of <italic>S. aureus</italic> and therefore, could provide better infection models than previously assumed. Pre-exposure to the bacteria is a possible confounder in <italic>S. aureus</italic> infection and vaccination studies and should be monitored.</p>