Laboratory Mice Are Frequently Colonized with and Mount a Systemic Immune Response-Note of Caution for Infection Experiments.

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