The protease SplB of Staphylococcus aureus targets host complement components and inhibits complement-mediated bacterial opsonophagocytosis.

Dasari P, Nordengrün M, Vilhena C, Steil L, Abdurrahman G, Surmann K, Dhople V, Lahrberg J, Bachert C, Skerka C, Völker U, Bröker BM, Zipfel PF (2021) The protease SplB of Staphylococcus aureus targets host complement components and inhibits complement-mediated bacterial opsonophagocytosis. J Bacteriol 204(1), e0018421.

Abstract

Staphylococcus aureus is an opportunistic pathogen that can cause life-threatening infections, particularly in immunocompromised individuals. The high-level virulence of S. aureus largely relies on its diverse and variable collection of virulence factors and immune-evasion proteins, including the six serine protease-like proteins SplA-SplF. Spl proteins are expressed by most clinical isolates of S. aureus, but little is known about the molecular mechanisms by which these proteins modify the host’s immune response for the benefit of the bacteria. Here, we identify SplB as a protease that inactivates central human complement proteins, i.e., C3, C4, and the activation fragments C3b and C4b, by preferentially cleaving their α-chains. SplB maintained its proteolytic activity in human serum, degrading C3 and C4. SplB further cleaved the components of the terminal complement pathway, C5, C6, C7, C8, and C9. By contrast, the important soluble human complement regulators, Factor H and C4BP, as well as C1q, were left intact. Thereby SplB reduced C3b-mediated opsonophagocytosis by human neutrophils as well as C5b-9 deposition on the bacterial surface. In conclusion, we identified the first physiological substrates of the S. aureus extracellular protease SplB. This enzyme inhibits all three complement pathways and blocks opsonophagocytosis. Thus, SplB can be considered as a novel staphylococcal complement-evasion protein.

Leibniz-HKI-Autor*innen

Prasad Dasari
Christine Skerka
Cláudia S. J. Vilhena
Peter F. Zipfel

Identifier

doi: 10.1128/JB.00184-21

PMID: 34633872