PepO and CppA modulate Streptococcus sanguinis susceptibility to complement immunity and virulence

Author(s)

Alves, Livia A. ; Naveed, Hassan ; Franco, Eduardo M. ; Garcia, Maira Terra ; Freitas, Victor A. ; Junqueira, Juliana C. ; Bastos, Debora C. ; Araujo, Thais L. S. ; Chen, Tsute ; Mattos-Graner, Renata O.

• Document type: Journal article
• Source: VIRULENCE; v. 14, n. 1, p. 16-pg., 2023-12-31.

Abstract

Streptococcus sanguinis is a ubiquitous commensal species of the oral cavity commonly involved as an opportunistic pathogen in cardiovascular infections. In this study, we investigated the functions of endopeptidase O (PepO) and a C3-degrading protease (CppA) in the systemic virulence of S. sanguinis. Isogenic mutants of pepO and cppA obtained in strain SK36 showed increased susceptibility to C3b deposition and to opsonophagocytosis by human polymorphonuclear neutrophils (PMN). These mutants differ, however, in their profiles of binding to serum amyloid P component (SAP) and C1q, whereas both showed reduced interaction with C4b-binding protein (C4BP) and/or factor H (FH) regulators as compared to SK36. The two mutants showed defects in ex vivo persistence in human blood, serum-mediated invasion of HCAEC endothelial cells, and virulence in a Galleria mellonella infection model. The transcriptional activities of pepO and cppA, assessed by RT-qPCR in nine wild-type strains, further indicated strain-specific profiles of pepO/cppA expression. Moreover, non-conserved amino acid substitutions were detected among the strains, mostly in CppA. Phylogenetic comparisons with homologues of streptococcal species of the oral and oropharyngeal sites suggested that S. sanguinis PepO and CppA have independent ancestralities. Thus, this study showed that PepO and CppA are complement evasion proteins expressed by S. sanguinis in a strain-specific manner, which are required for multiple functions associated with cardiovascular virulence. (AU)

• FAPESP's process: 17/19899-4 - Identification of factors modulating the susceptibility of Streptococcus sanguinis to complement immunity
• Grantee: Lívia Araújo Alves
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/20435-8 - Molecular chaperone HSP70 mediates proteostasis in endothelial cells response to hemodynamic force
• Grantee: Thaís Larissa Araujo de Oliveira Silva
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 18/12248-0 - The role of exopolysaccharides and extracellular DNA in Streptococcus sanguinis evasion to complement system
• Grantee: Victor Aragão Abreu de Freitas
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 18/02054-4 - Identification of factors modulating the susceptibility of Streptococcus sanguinis to complement immunity
• Grantee: Renata de Oliveira Mattos Graner
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/13739-8 - Molecular chaperone HSP70 mediates proteostasis in endothelial cells response to hemodynamic force
• Grantee: Thaís Larissa Araujo de Oliveira Silva
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 21/13074-9 - Identification of genes of Streptococcus sanguinis involved in its capacity to invade, persist and functionally affect human endothelial cells
• Grantee: Renata de Oliveira Mattos Graner
• Support Opportunities: Regular Research Grants