Galectin-3 Is a Target for Proteases Involved in the Virulence of Staphylococcus aureus.

Abstract

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 β-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.

• Authors: Jonas Elmwall, Jakub Kwiecinski, Manli Na, Abukar Ahmed Ali, Veronica Osla, Lindsey N Shaw, Wanzhong Wang, Karin Sävman, Elisabet Josefsson, Johan Bylund, Tao Jin, Amanda Welin, Anna Karlsson
• Journal: Infection and immunity (Infect Immun) Vol. 85 Issue 7 (07 2017) ISSN: 1098-5522 [Electronic] United States
• PMID: 28438975 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 American Society for Microbiology.

Chemical References

• Bacterial Proteins
• Blood Proteins
• Galectin 3
• Galectins
• LGALS3 protein, human
• Serine Endopeptidases
• sspB protein, Staphylococcus aureus

Topics

• Animals
• Bacterial Load
• Bacterial Proteins (metabolism)
• Blood Proteins
• Disease Models, Animal
• Galectin 3 (metabolism)
• Galectins
• Host-Pathogen Interactions
• Humans
• Mice, Inbred C57BL
• Mice, Knockout
• Proteolysis
• Serine Endopeptidases (metabolism)
• Staphylococcal Skin Infections (microbiology, pathology)
• Staphylococcus aureus (enzymology, pathogenicity)
• Virulence