Galectin-3 Is a Target for Proteases Involved in the Virulence of Staphylococcus aureusShow others and affiliations
2017 (English)In: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 85, no 7, article id e00177-17Article in journal (Refereed) Published
Abstract [en]
Staphylococcus aureus is a major cause of skin and soft tissue infection. The bacterium expresses four major proteases that are emerging as virulence factors: aureolysin (Aur), V8 protease (SspA), staphopain A (ScpA), and staphopain B (SspB). We hypothesized that human galectin-3, a beta-galactoside-binding lectin involved in immune regulation and antimicrobial defense, is a target for these proteases and that proteolysis of galectin-3 is a novel immune evasion mechanism. Indeed, supernatants from laboratory strains and clinical isolates of S. aureus caused galectin-3 degradation. Similar proteolytic capacities were found in Staphylococcus epidermidis isolates but not in Staphylococcus saprophyticus. Galectin-3-induced activation of the neutrophil NADPH oxidase was abrogated by bacterium-derived proteolysis of galectin-3, and SspB was identified as the major protease responsible. The impact of galectin-3 and protease expression on S. aureus virulence was studied in a murine skin infection model. In galectin-3 (+)/(+) mice, SspB-expressing S. aureus caused larger lesions and resulted in higher bacterial loads than protease-lacking bacteria. No such difference in bacterial load or lesion size was detected in galectin-3 (+)/(+) mice, which overall showed smaller lesion sizes than the galectin-3 (+)/(+) animals. In conclusion, the staphylococcal protease SspB inactivates galectin-3, abrogating its stimulation of oxygen radical production in human neutrophils and increasing tissue damage during skin infection.
Place, publisher, year, edition, pages
American Society for Microbiology , 2017. Vol. 85, no 7, article id e00177-17
Keywords [en]
galectin-3, Staphylococcus aureus, neutrophils, protease, staphopain, skin infection, virulence, virulence regulation, virulence factors
National Category
Immunology in the medical area Infectious Medicine
Identifiers
URN: urn:nbn:se:umu:diva-139157DOI: 10.1128/IAI.00177-17ISI: 000408249700007OAI: oai:DiVA.org:umu-139157DiVA, id: diva2:1140270
2017-09-112017-09-112018-06-09Bibliographically approved