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The two-component system VicRK regulates functions associated with Streptococcus mutans resistance to complement immunity.
Alves, Livia A; Harth-Chu, Erika N; Palma, Thais H; Stipp, Rafael N; Mariano, Flávia S; Höfling, José F; Abranches, Jacqueline; Mattos-Graner, Renata O.
Afiliação
  • Alves LA; Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil.
  • Harth-Chu EN; Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil.
  • Palma TH; Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil.
  • Stipp RN; Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil.
  • Mariano FS; Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil.
  • Höfling JF; Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil.
  • Abranches J; Department of Oral Biology, College of Dentistry - University of Florida, Gainesville, FL, USA.
  • Mattos-Graner RO; Department of Oral Diagnosis, Piracicaba Dental School - State University of Campinas, Piracicaba, SP, Brazil.
Mol Oral Microbiol ; 32(5): 419-431, 2017 10.
Article em En | MEDLINE | ID: mdl-28382721
Streptococcus mutans, a dental caries pathogen, can promote systemic infections upon reaching the bloodstream. The two-component system (TCS) VicRKSm 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 VicRKSm affects S. mutans susceptibility to blood-mediated immunity. Compared with parent strain UA159, the vicKSm 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 vicKSm -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 VicRKSm.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Streptococcus mutans / Proteínas de Bactérias / Complemento C3b / Regulação Bacteriana da Expressão Gênica / Evasão da Resposta Imune Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Revista: Mol Oral Microbiol Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Dinamarca
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Streptococcus mutans / Proteínas de Bactérias / Complemento C3b / Regulação Bacteriana da Expressão Gênica / Evasão da Resposta Imune Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Revista: Mol Oral Microbiol Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Brasil País de publicação: Dinamarca