Chemotaxis Inhibitory Protein of <i>Staphylococcus aureus</i>, a Bacterial Antiinflammatory Agent

TLDR

Leukocyte migration is central to host defense and inflammation, and bacteria generate chemoattractants such as formylated peptides, C5a, and leukotriene B4 to recruit these cells. The study aims to characterize a novel Staphylococcus aureus protein that impairs neutrophil and monocyte responses to formylated peptides and C5a. This protein, secreted by S. aureus, specifically blocks neutrophil and monocyte chemotaxis toward formylated peptides and C5a.

Abstract

Leukocyte migration is a key event both in host defense against invading pathogens as well as in inflammation. Bacteria generate chemoattractants primarily by excretion (formylated peptides), complement activation (C5a), and subsequently through activation of leukocytes (e.g., leukotriene B4, platelet-activating factor, and interleukin 8). Here we describe a new protein secreted by Staphylococcus aureus that specifically impairs the response of neutrophils and monocytes to formylated peptides and C5a. This chemotaxis inhibitory protein of S. aureus (CHIPS) is a 14.1-kD protein encoded on a bacteriophage and is found in >60% of clinical isolates. CHIPS reduces the neutrophil recruitment toward C5a in a mouse peritonitis model, even though its activity is much more potent on human than on mouse cells. These findings suggest a new immune escape mechanism of S. aureus and put forward CHIPS as a potential new antiinflammatory therapeutic compound.