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Identification of factors modulating the susceptibility of Streptococcus sanguinis to complement immunity

Abstract

Streptococcus sanguinis (Ss) is a pioneer species of teeth, which inhibits pathogenic species of dental biofilms, but is frequently involved in infective endocarditis through mechanisms as yet unknown. Our recent results indicate that S. sanguinis has low susceptibility to deposition of C3b/iC3b of the complement system, a major opsonin involved in blood clearance by neutrophils (PMN). The aim of this project is to investigate the molecular mechanisms involved in S. sanguinis resistance to complement-mediated opsonization. To this end, S. sanguinis strains isolated from dental plaque and from the bloodstream will be characterized regarding their binding to C3b/iC3b and to serum proteins which activate (SAP, C1q, ficolina L) or inhibit (C4BP, Fator H, FHL1 e C1-INH) the complement. Genes potentially involved in these phenotypes will be then investigated, including covRSs, which encodes the transcriptional regulator CovR typically involved in the regulation of genes for complement evasion in streptococci. Genes likely regulated by CovRSs, which are potentially involved in complement evasion (pepOSs and cppASs) will be also investigated. Transcript levels of covRSs, pepOSs and cppASs will be compared between the isolates by RT-qPCR. Additionally, isogenic mutants of these genes will be obtained in strain SK36, and characterized regarding their binding to C3b and to soluble proteins involved in activation or inhibition of the complement, and to fibronectin. Mutant strains with altered phenotypes will be then compared to parent strain regarding their susceptibilities to opsonophagocytosis by PMN from human blood. The results of this project may help to elucidate mechanisms which modulate S. sanguinis susceptibility to complement-mediated immunity, an important topic for the development of therapies to control systemic infections by this species. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
HARTH-CHU, ERIKA N.; ALVES, LIVIA A.; THEOBALDO, JESSICA D.; SALOMAO, MARIANA F.; HOFLING, JOSE F.; KING, WILLIAM F.; SMITH, DANIEL J.; MATTOS-GRANER, RENATA O. PcsB Expression Diversity Influences on Streptococcus mitis Phenotypes Associated With Host Persistence and Virulence. FRONTIERS IN MICROBIOLOGY, v. 10, NOV 12 2019. Web of Science Citations: 0.
ALVES, LIVIA A.; DE CARLI, THAIS R.; HARTH-CHU, ERIKA N.; MARIANO, FLAVIA S.; HOFLING, JOSE F.; STIPP, RAFAEL N.; MATTOS-GRANER, RENATA O. Oral streptococci show diversity in resistance to complement immunity. Journal of Medical Microbiology, v. 68, n. 4, p. 600-608, APR 2019. Web of Science Citations: 2.

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