AbstractBackgroundWhether mice are an appropriate model forS.aureusinfection and vaccination studies is a matter of debate, because they are not considered as natural hosts ofS. aureus.Sparked by an outbreak of S.aureusinfections in laboratory mice, we investigated whether laboratory mice are commonly colonized with S.aureusand whether this might impact on infection experiments.MethodsWe characterized 99S. aureusisolates from laboratory mice (spatyping, virulence gene PCR), and quantified murine antibodies using FlexMap technology.ResultsSpecific-pathogen-free mice from various vendors were frequently colonized withS. aureus(0-21%).S. aureuswas readily transmitted from murine parents to offspring, which became persistently colonized. Most murine isolates belonged to the lineage CC88 (54%). Murine strains showed features of host adaptation, such as absence ofhlb-converting phages and superantigen genes, as well as enhanced coagulation of murine plasma. Importantly,S. aureuscolonization induced a systemic IgG response specific for numerousS. aureusproteins, including several vaccine candidates.ConclusionLaboratory mice are natural hosts ofS. aureusand, therefore, provide better infection models than previously assumed. Pre-exposure to S.aureusis a possible confounder inS. aureusinfection and vaccination studies.