Virulence of a hemB mutant displaying the phenotype of a Staphylococcus aureus small colony variant in a murine model of septic arthritis |
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| Authors: | Jonsson Ing-Marie von Eiff Christof Proctor Richard A Peters Georg Rydén Cecilia Tarkowski Andrzej |
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| Institution: | 1. Department of Rheumatology, University of Göteborg, Guldhedsgatan 10A, S-413 46 Göteborg, Sweden;2. Institute of Medical Microbiology, University of Münster, Germany;3. Departments of Medicine and Medical Microbiology/Immunology, University of Wisconsin, Madison, WI, USA;4. Departments of Medical Biochemistry and Microbiology and Infectious Diseases, University of Uppsala, Uppsala, Sweden;1. Immunoallergy Department, Coimbra Hospital Universitary Centre, Coimbra, Portugal;2. Immunoallergy Department, CUF Descobertas Hospital, Lisbon, Portugal;1. Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;2. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan;3. Emergency Department, Taipei Veterans General Hospital, Taipei, Taiwan;4. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli County, Taiwan;5. Clinical Microbiology Laboratory Division of Clinical Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;6. Department of Nursing, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan;7. School of Nursing, National Yang-Ming University, Taipei, Taiwan;8. Division of Infectious Diseases, Cheng-Hsin General Hospital, Taipei, Taiwan |
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| Abstract: | Persistence of Staphylococcus aureus during invasive infections has been associated with a small-colony variant (SCV) phenotype. SCVs are frequently auxotrophic for menadione or hemin, two compounds involved in the biosynthesis of the electron transport chain. SCVs have been shown to be more resistant to antibiotics such as aminoglycosides, grow slowly and persist intracellularly. The aim of this study was to assess the virulence of an hemB mutant, which has been shown to display the typical characteristics of clinical SCVs, in a murine model of septic arthritis. NMRI mice were inoculated intravenously with either the wild type strain Newman or with its mutant displaying the SCV phenotype. The clinical, bacteriological, and histopathological progression of the disease was studied. Mice inoculated with the hemB mutant displayed a higher frequency and a significantly higher severity of arthritis than mice inoculated with the wild type Newman strain. Despite that, the mutant inoculated mice displayed significantly lower bacterial burden in their kidneys and joints compared with mice exposed to the wild parental strain. Notably, the hemB mutant produced almost 20 times more protease in vitro than the parental strain. We conclude that the small colony variants of S. aureus are more virulent on a per organism basis than its isogenic parental strain in the model of septic arthritis. This can at least in part be explained by the ability of SCV to produce high amounts of destructive proteases. |
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