The two-component system VicRK regulates functions associated with Streptococcus mutans resistance to complement immunity

Autor(es)

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.

• Tipo de documento: Artigo Científico
• Fonte: Molecular Oral Microbiology; v. 32, n. 5, p. 419-431, OCT 2017.
• Citações Web of Science: 12

Resumo

Streptococcus mutans, a dental caries pathogen, can promote systemic infections upon reaching the bloodstream. The two-component system (TCS) VicRK(Sm) of S.mutans regulates the synthesis of and interaction with sucrose-derived exopolysaccharides (EPS), processes associated with oral and systemic virulence. In this study, we investigated the mechanisms by which VicRK(Sm) affects S.mutans susceptibility to blood-mediated immunity. Compared with parent strain UA159, the vicK(Sm) isogenic mutant (UAvic) showed reduced susceptibility to deposition of C3b of complement, low binding to serum immunoglobulin G (IgG), and low frequency of C3b/IgG-mediated opsonophagocytosis by polymorphonuclear cells in a sucrose-independent way (P<.05). Reverse transcriptase quantitative polymerase chain reaction analysis comparing gene expression in UA159 and UAvic revealed that genes encoding putative peptidases of the complement (pepO and smu.399) were upregulated in UAvic in the presence of serum, although genes encoding murein hydrolases (SmaA and Smu.2146c) or metabolic/surface proteins involved in bacterial interactions with host components (enolase, GAPDH) were mostly affected in a serum-independent way. Among vicK(Sm)-downstream genes (smaA, smu.2146c, lysM, atlA, pepO, smu.399), only pepO and smu.399 were associated with UAvic phenotypes; deletion of both genes in UA159 significantly enhanced levels of C3b deposition and opsonophagocytosis (P<.05). Moreover, consistent with the fibronectin-binding function of PepO orthologues, UAvic showed increased binding to fibronectin. Reduced susceptibility to opsonophagocytosis was insufficient to enhance ex vivo persistence of UAvic in blood, which was associated with growth defects of this mutant under limited nutrient conditions. Our findings revealed that S.mutans employs mechanisms of complement evasion through peptidases, which are controlled by VicRK(Sm.</IN) (AU)

• Processo FAPESP: 15/12940-3 - Identificação de proteínas de superfície de Streptococcus mutans implicadas no escape à opsonização pelo sistema complemento
• Beneficiário: Renata de Oliveira Mattos Graner
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/04222-5 - Estudo da participação dos reguladores de transcrição gênica VicRK e CovR na susceptibilidade de Streptococcus mutans à opsonização pelo sistema complemento.
• Beneficiário: Lívia Araújo Alves
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 09/50547-0 - Characterization of GbpB/PcsB homologues in commensal species of oral streptococci
• Beneficiário: Erika Nikitza Shiauha Harth Chu
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/50966-6 - Estudo da participação dos reguladores de transcrição gênica VicRK e CovR na susceptibilidade de Streptococcus mutans e Streptococcus sanguinis a opsonização pelo sistema completo
• Beneficiário: Renata de Oliveira Mattos Graner
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/07237-1 - Identificação de proteínas de superfície de Streptococcus mutans implicadas no escape à opsonização pelo sistema complemento
• Beneficiário: Lívia Araújo Alves
• Modalidade de apoio: Bolsas no Brasil - Doutorado