Abstract
Whether mice are an appropriate model for S. aureus infection and vaccination studies is a matter of debate, because they are not considered as natural hosts of S. aureus. We previously identified a mouse-adapted S. aureus strain, which caused infections in laboratory mice. This raised the question whether laboratory mice are commonly colonized with S. aureus and whether this might impact on infection experiments. Publicly available health reports from commercial vendors revealed that S. aureus colonization is rather frequent, with rates as high as 21% among specific-pathogen-free mice. In animal facilities, S. aureus was readily transmitted from parents to offspring, which became persistently colonized. Among 99 murine S. aureus 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 S. aureus isolates revealed features of host adaptation. In detail, murine strains lacked hlb-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, S. aureus colonization clearly primed the murine immune system, inducing a systemic IgG response specific for numerous S. aureus proteins, including several vaccine candidates. Phospholipase C emerged as a promising test antigen for monitoring S. aureus colonization in laboratory mice. In conclusion, laboratory mice are natural hosts of S. aureus and therefore, could provide better infection models than previously assumed. Pre-exposure to the bacteria is a possible confounder in S. aureus infection and vaccination studies and should be monitored.
Highlights
Staphylococcus aureus is a dangerous opportunistic pathogen, a leading cause of bacterial infection in hospitals and in the community world-wide, and a prominent example of the crisis of antibiotic resistance (World Health Organization, 2014)
The European branches of Janvier, Charles River, and Envigo do not report the S. aureus status of SPF mice as this is not recommended for immunocompetent mice in health monitoring guidelines promulgated by the Federation of Laboratory Animal Science Associations (FELASA; Mahler Convenor et al, 2014)
Our findings suggest that murine S. aureus isolates have adapted to their murine host by eliminating mobile genetic elements (MGEs) encoding human-specific virulence factors, such as immune evasion gene cluster (IEC)-encoding Sa3int phages and SAg-encoding MGEs
Summary
Staphylococcus aureus is a dangerous opportunistic pathogen, a leading cause of bacterial infection in hospitals and in the community world-wide, and a prominent example of the crisis of antibiotic resistance (World Health Organization, 2014). Mice are the most commonly used surrogate host to model S. aureus infection with the obvious advantages of a well-characterized immune system, the wide availability of well-characterized gene knock-out strains and of being relatively easy and inexpensive to breed. Whether mice are appropriate has often been questioned because there is broad consensus in the research community that mice are not natural hosts of S. aureus (Cuny et al, 2010; McCarthy and Lindsay, 2010; Capparelli et al, 2011; Mulcahy et al, 2012). Experimental colonization of mice with S. aureus is usually transient, and very high infection doses are routinely required (Kiser et al, 1999)
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