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The primary modes of transmission of <jats:italic>S. aureus<\/jats:italic> are via direct contact with a colonized or infected individual or invasive spread from a colonization niche in the same individual. <jats:italic>S. aureus<\/jats:italic> can cause a myriad of diseases, including skin and soft tissue infections (SSTIs), osteomyelitis, pneumonia, endocarditis, and sepsis. <jats:italic>S. aureus<\/jats:italic> infection is characterized by the formation of purulent lesions known as abscesses, which are rich in live and dead neutrophils, macrophages, and surrounded by a capsule containing fibrin and collagen. Different strains of <jats:italic>S. aureus<\/jats:italic> produce varying amounts of toxins that evade and\/or elicit immune responses. Therefore, animal models of <jats:italic>S. aureus<\/jats:italic> infection provide a unique opportunity to understand the dynamics of organ\u2010specific immune responses and modifications in the pathogen that could favor the establishment of the pathogen. With advances in in vivo imaging of fluorescent transgenic mice, combined with fluorescent\/bioluminescent bacteria, we can use mouse models to better understand the immune response to these types of infections. By understanding the host and bacterial dynamics within various organ systems, we can develop therapeutics to eliminate these pathogens. This module describes in vivo mouse models of both local and systemic <jats:italic>S. aureus<\/jats:italic> infection. \u00a9 2021 Wiley Periodicals LLC.<\/jats:p><jats:p>This article was corrected on 20 July 2022. See the end of the full text for details.<\/jats:p><jats:p><jats:bold>Basic Protocol 1<\/jats:bold>: Murine model of <jats:italic>Staphylococcus aureus<\/jats:italic> subcutaneous infection<\/jats:p><jats:p><jats:bold>Alternate Protocol<\/jats:bold>: Murine tape stripping skin infection model<\/jats:p><jats:p><jats:bold>Basic Protocol 2<\/jats:bold>: Sample collection to determine skin structure, production of inflammatory mediators, and bacterial load<\/jats:p><jats:p><jats:bold>Basic Protocol 3<\/jats:bold>: Murine model of post\u2010traumatic <jats:italic>Staphylococcus aureus<\/jats:italic> osteomyelitis<\/jats:p><jats:p><jats:bold>Basic Protocol 4<\/jats:bold>: Intravenous infection of the retro\u2010orbital sinus<\/jats:p><jats:p><jats:bold>Support Protocol<\/jats:bold>: Preparation of the bacterial inoculum<\/jats:p>","DOI":"10.1002\/cpz1.52","type":"journal-article","created":{"date-parts":[[2021,3,3]],"date-time":"2021-03-03T13:16:40Z","timestamp":1614777400000},"source":"Crossref","is-referenced-by-count":34,"title":["Murine Models for Staphylococcal Infection"],"prefix":"10.1002","volume":"1","author":[{"given":"Nathan","family":"Klopfenstein","sequence":"first","affiliation":[{"name":"Division of Infectious Disease, Department of Medicine Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Cassat","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Department of Pediatrics, Division of Pediatric Infectious Diseases Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Vanderbilt Center for Bone Biology Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Department of Biomedical Engineering Vanderbilt University  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Monteith","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anderson","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney","family":"Drury","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Skaar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology Vanderbilt University Medical Center  Nashville Tennessee"},{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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