Involvement of lipoprotein PpiA of Streptococcus gordonii in evasion of phagocytosis by macrophages

Abstract

Streptococcus gordonii is a commensal gram-positive bacterium that resides in the human oral cavity, and is one of the most common causes of infective endocarditis (IE). Bacterial surface molecules play an important role in establishing IE, and several S. gordonii proteins have been implicated in binding to host cells during the establishment of IE. In this study, we identified a putative lipoprotein, peptidyl-prolyl cis/trans isomerase (PpiA), and clarified its role in evasion of phagocytosis by macrophages. Attenuation of the gene encoding prolipoprotein diacylglyceryl transferase (Lgt) altered the localization of PpiA from the cell surface to the culture supernatant, indicating that PpiA is lipid-anchored in the cell membrane by Lgt. Both human and murine macrophages showed higher phagocytic activity towards ppiA and lgt mutants than the wild-type, indicating that the presence of PpiA suppresses phagocytosis of S. gordonii. Human macrophages treated with dextran sulfate had significantly impaired phagocytosis of S. gordonii, suggesting that class A scavenger receptors in human macrophages are involved in the phagocytosis of S. gordonii. These results provide evidence that S. gordonii lipoprotein PpiA plays an important role in inhibiting phagocytic engulfment and in evasion of the host immune response.

An Intracellular Peptidyl-Prolyl cis / trans Isomerase Is Required for Folding and Activity of the Staphylococcus aureus Secreted Virulence Factor Nuclease

“…Although cyclophilins are known to exist in bacteria, their functions remain largely unexplored. Those that have been studied are typically cell wall-associated lipoproteins (11,12), and there are very few reports on the role of cytoplasmic cyclophilins in bacteria. One known example of a cytoplasmic cyclophilin is the PpiB protein from B. subtilis (39).…”

“…The cyclophilins are by far the least-studied and least well understood group of PPIases in bacteria. Those that have been studied are typically lipoproteins (similar to PrsA) and are thought to function is a similar way (11,12). However, in silico analysis reveals that cytoplasmic cyclophilins are predicted to exist in the genomes of a number of bacterial species, although no function has been demonstrated for these.…”

The Intracellular Cyclophilin PpiB Contributes to the Virulence of Staphylococcus aureus Independently of Its Peptidyl-Prolyl cis/trans Isomerase Activity

“…folding of secreted virulence factors (11,(26)(27)(28)(29). Previous work by our group on the S. aureus cyclophilin PpiB demonstrated that PpiB is a functional PPIase, that it affects the refolding and activity of the virulence factor Nuc, and that it contributes to hemolytic activity (8).…”

Survival in amoeba—a major selection pressure on the presence of bacterial copper and zinc resistance determinants? Identification of a “copper pathogenicity island”

“…Whether CueO is regulated by the adjacent two-component system or CopY is not known. In this genome region, there are also several putative copper chaperones and a prolipoprotein diacylglyceryl transferase, which has been associated with virulence (Cho et al 2013;Reffuveille et al 2012) (Fig. 3).…”