Analysis of the roles of the transcriptional regulators VicRK and CovR in the susceptibility of Streptococcus mutans to opsonization by the complement system.

• Grant number: 12/04222-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: June 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Renata de Oliveira Mattos Graner
• Grantee: Lívia Araújo Alves
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Streptococcus mutans (SM) is a common bacterial species of the oral cavity of humans, which represent major pathogens of dental caries, and which are involved in bacteremia leading to infectious endocarditis (Nakano et al., 2009). Although the major ecological niches of SM are the supra-gingival tooth surfaces, these organisms also colonize the gingival crevice, mucosal surfaces and access cytoplasmic sites of oral epithelial cells (Rudney et al., 2005), where they encounter host immune factors. To persist in the oral cavity or in the blood stream, SM need to survive to immune factors present in saliva, oral tissues or blood, and to physiologically adapt to biophysical conditions of the colonized sites (Negrini et al., 2011). This complex process involves several modifications in the SM transcriptome in response to the environmental stimuli, which are mainly coordinated by two component systems (TCS) for global gene regulation. TCS are comprised by a sensor histidine kinase (HK) in the cell membrane, which is auto-phosphorylated after activation by an environmental signal. The HK then transfer the phosphate group to an intracellular cognate response regulator, which in turn is activated to interact with promoter sequences of the target genes (Raghavan & Groisman, 2010). SM have the TCS VicRK (Vic de virulence control), and the orphan RR CovR (cov de control of virulence), which regulate factors implicated in virulence for caries development (Smith & Spatafora, 2011). In patogenic species of streptococci, VicRK e CovR regulate genes for evasion of host immune factors (Mitchell, 2003). This seems to also occur in SM (Negrini et al., 2012). The aim of this project is to investigate the roles of VicRK and CovR in the SM susceptibility to opsonization by the complement system, an important component of the immune system that controls bacterial infection. To that purpose, knock-out mutants of vicK and covR obtained in SM strain UA159 will be caracterized regarding binding of complement C3b/iC3b in the presence or not of antibodies. The effects of complement binding in SM strain phagocytosis by human PMN will be then investigated.

Scientific publications

(6)

(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)

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. (15/12940-3, 12/04222-5, 09/50547-0, 12/50966-6, 15/07237-1)

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. (18/02054-4, 13/07098-6, 15/12940-3, 09/50547-0, 12/04222-5, 12/50966-6, 15/07237-1, 17/19899-4)

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. (15/12940-3, 09/50547-0, 15/07237-1, 12/51832-3, 12/04222-5)

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. (17/19899-4, 15/12940-3, 12/04222-5, 18/02054-4, 15/07237-1, 09/50547-0, 12/50966-6)

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. (15/12940-3, 12/04222-5, 09/50547-0, 15/07237-1)

MATTOS-GRANER, RENATA O.; KLEIN, MARLISE I.; ALVES, LIVIA ARAUJO. The complement system as a key modulator of the oral microbiome in health and disease. CRITICAL REVIEWS IN MICROBIOLOGY, v. N/A, p. 30-pg., 2023-01-05. (12/04222-5, 21/13074-9, 15/12940-3, 16/17216-4, 12/50966-6, 12/51832-3, 17/19899-4, 21/06801-1, 18/02054-4, 15/07237-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ALVES, Lívia Araújo. Analysis of the roles of the transcriptonal regulators VicRK and CovR in the susceptibility of Streptococcus mutans to opsonization by the complement system. 2014. Master's Dissertation - Universidade Estadual de Campinas (UNICAMP). Faculdade de Odontologia de Piracicaba Piracicaba, SP.