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Identification of surface proteins of Streptococcus mutans involved in evasion of opsonization by the complement system

Grant number: 15/12940-3
Support type:Regular Research Grants
Duration: September 01, 2015 - February 28, 2018
Field of knowledge:Health Sciences - Dentistry
Principal researcher:Renata de Oliveira Mattos Graner
Grantee:Renata de Oliveira Mattos Graner
Home Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
Assoc. researchers:Erika Nikitza Shiauha Harth Chu

Abstract

Streptococcus mutans (SM) is a common bacterial species of the oral cavity of humans involved in the pathogenesis of dental caries, which can promote bacterial endocarditis after gaining access to the bloodstream. Little is known about the virulence factors involved in the ability of this species to survive in the bloodstream to cause systemic infections. During the process of colonization and/or infection of the host, SM undergoes several changes in its transcriptome in response to environmental stimuli, which are in part, controlled by transcriptional regulatory two-component systems (TCS). TCSs are typically composed by a sensor histidine kinase membrane protein (K) and an intracellular transcription factor (response regulator; R). In SM, the TCS VicRK and the orphan regulator CovR (a R without its cognate K protein) regulate virulence genes associated with the formation of cariogenic biofilms and evasion of phagocytosis by PMN of human blood. Recently, we found that the inactivation of genes encoding VicK (vicK) or CovR (covR) in strain UA159 impairs deposition of C3b/iC3b of the complement system, major blood opsonins. Because VicRK and CovR regulate genes encoding surface proteins (which includes wapE, lysM, smu2146c, smaA and epsC), it is likely that some of these genes directly or indirectly influence on deposition of C3b/iC3b on the bacterial surface. Additionally, other genes in genomic loci apparently regulated by VicRK and CovR, encode orthologues of C3-proteases [smu.399 and pepO (smu.2036)] or proteins which potentially influence on deposition of C3b (smu.1247 and smu.360). The aim of this project is to identify surface proteins of SM directly or indirectly regulated by the TCS VicRK and/or CovR, which affects deposition of C3b/iC3b of the human complement system. To this end, intensities of C3b/iC3b deposition on bacterial surface and phagocytosis of opsonized strains by PMN will be determined in knockout mutants of genes wapE, lysM, 2146c, smaA, epsC, smu.399 and pepO, and compared with the parental strain UA159. The capacities to adsorb soluble blood components (fibronectin, plasminogen and fibrinogen), which influence on the deposition of C3b/iC3b, will be also compared between the same strains. Moreover, the expression of VicRK/CovR-regulated genes in response to SM exposure to human serum will be determined. The identification of SM surface components which influence on opsonization by the complement system may contribute to the development of therapies to control bacteremia and systemic infections by this bacterial species. (AU)

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Scientific publications (8)
(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.
ALVES, LIVIA ARAUJO; GANGULY, TRIDIB; MATTOS-GRANER, RENATA O.; KAJFASZ, JESSICA; HARTH-CHU, ERIKA N.; LEMOS, JOSE A.; ABRANCHES, JACQUELINE. CovR and VicRKX Regulate Transcription of the Collagen Binding Protein Cnm of Streptococcus mutans. Journal of Bacteriology, v. 200, n. 23 DEC 2018. Web of Science Citations: 1.
CAMARGO, TARSILA M.; STIPP, RAFAEL N.; ALVES, LIVIA A.; HARTH-CHU, ERIKA N.; HOFLING, JOSE F.; MATTOS-GRANER, RENATA O. Novel Two-Component System of Streptococcus sanguinis Affecting Functions Associated with Viability in Saliva and Biofilm Formation. Infection and Immunity, v. 86, n. 4 APR 2018. Web of Science Citations: 7.
MATTOS-GRANER, RENATA O.; DUNCAN, MARGARET J. Two-component signal transduction systems in oral bacteria. JOURNAL OF ORAL MICROBIOLOGY, v. 9, NOV 27 2017. Web of Science Citations: 11.
ALVES, LIVIA A.; HARTH-CHU, ERIKA N.; PALMA, THAIS H.; STIPP, RAFAEL N.; MARIANO, FLAVIA S.; HOEFLING, JOSE F.; ABRANCHES, JACQUELINE; MATTOS-GRANER, RENATA O. The two-component system VicRK regulates functions associated with Streptococcus mutans resistance to complement immunity. Molecular Oral Microbiology, v. 32, n. 5, p. 419-431, OCT 2017. Web of Science Citations: 12.
PALMA, THAIS H.; HARTH-CHU, ERIKA N.; SCOTT, JODIE; STIPP, RAFAEL N.; BOISVERT, HEIKE; SALOMAO, MARIANA F.; THEOBALDO, JESSICA D.; POSSOBON, ROSANA F.; NASCIMENTO, LEANDRO C.; MCCAFFERTY, JONATHAN W.; FALLER, LINA; DUNCAN, MARGARET J.; MATTOS-GRANER, RENATA O. Oral cavities of healthy infants harbour high proportions of Streptococcus salivarius strains with phenotypic and genotypic resistance to multiple classes of antibiotics. Journal of Medical Microbiology, v. 65, n. 12, p. 1456-1464, DEC 2016. Web of Science Citations: 4.
ALVES, LIVIA A.; NOMURA, RYOTA; MARIANO, FLVIA S.; HARTH-CHU, ERIKA N.; STIPP, RAFAEL N.; NAKANO, KAZUHIKO; MATTOS-GRANER, RENATA O. CovR Regulates Streptococcus mutans Susceptibility To Complement Immunity and Survival in Blood. Infection and Immunity, v. 84, n. 11, p. 3206-3219, NOV 2016. Web of Science Citations: 7.

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