Artículos de revistas
Covr Regulates Streptococcus Mutans Susceptibility To Complement Immunity And Survival In Blood
Registro en:
Infection And Immunity. Amer Soc Microbiology, v. 84, p. 3206 - 3219, 2016.
0019-9567
1098-5522
WOS:000389902300012
10.1128/IAI.00406-16
Autor
Alves
Livia A.; Nomura
Ryota; Mariano
Flvia S.; Harth-Chu
Erika N.; Stipp
Rafael N.; Nakano
Kazuhiko; Mattos-Graner
Renata O.
Institución
Resumen
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Streptococcus mutans, a major pathogen of dental caries, may promote systemic infections after accessing the bloodstream from oral niches. In this study, we investigate pathways of complement immunity against S. mutans and show that the orphan regulator CovR (CovR(Sm)) modulates susceptibility to complement opsonization and survival in blood. S. mutans blood isolates showed reduced susceptibility to C3b deposition compared to oral isolates. Reduced expression of covRSm in blood strains was associated with increased transcription of CovR(Sm)-repressed genes required for S. mutans interactions with glucans (gbpC, gbpB, and epsC), sucrose-derived exopolysaccharides (EPS). Consistently, blood strains showed an increased capacity to bind glucan in vitro. Deletion of covR(Sm) in strain UA159 (UAcov) impaired C3b deposition and binding to serum IgG and C-reactive protein (CRP) as well as phagocytosis through C3b/iC3b receptors and killing by neutrophils. Opposite effects were observed in mutants of gbpC, epsC, or gtfBCD (required for glucan synthesis). C3b deposition on UA159 was abolished in C1q-depleted serum, implying that the classical pathway is essential for complement activation on S. mutans. Growth in sucrose-containing medium impaired the binding of C3b and IgG to UA159, UAcov, and blood isolates but had absent or reduced effects on C3b deposition in gtfBCD, gbpC, and epsC mutants. UAcov further showed increased ex vivo survival in human blood in an EPS-dependent way. Consistently, reduced survival was observed for the gbpC and epsC mutants. Finally, UAcov showed an increased ability to cause bacteremia in a rat model. These results reveal that CovRSm modulates systemic virulence by regulating functions affecting S. mutans susceptibility to complement opsonization. 84 11 3206 3219 Japan Society for the Promotion of Science (JSPS) [15K11363] Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) (PNPD) Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2009/50547-0, 2012/50996-6, 2015/12940-3, 2012/04222-5, 2015/07237-1] Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)