PcsB Expression Diversity Influences on Streptococcus mitis Phenotypes Associated With Host Persistence and Virulence

Autor(es)

Harth-Chu, Erika N. ^[1] ; Alves, Livia A. ^[1] ; Theobaldo, Jessica D. ^[1] ; Salomao, Mariana F. ^[1] ; Hofling, Jose F. ^[1] ; King, William F. ^[2] ; Smith, Daniel J. ^[2] ; Mattos-Graner, Renata O. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Oral Diag, Piracicaba - Brazil

^[2] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA - USA

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 10, NOV 12 2019.
• Citações Web of Science: 0

Resumo

S. mitis is an abundant member of the commensal microbiota of the oral cavity and pharynx, which has the potential to promote systemic infections. By analyzing a collection of S. mitis strains isolated from the oral cavity at commensal states or from systemic infections (blood strains), we established that S. mitis ubiquitously express the surface immunodominant protein, PcsB (also called GbpB), required for binding to sucrose-derived exopolysaccharides (EPS). Immuno dot blot assays with anti-PcsB antibodies and RT-qPCR transcription analyses revealed strain-specific profiles of PcsB production associated with diversity in pcsB transcriptional activities. Additionally, blood strains showed significantly higher levels of PcsB expression compared to commensal isolates. Because Streptococcus mutans co-colonizes S. mitis dental biofilms, and secretes glucosyltransferases (GtfB/C/D) for the synthesis of highly insoluble EPS from sucrose, profiles of S. mitis binding to EPS, biofilm formation and evasion of the complement system were assessed in sucrose-containing BHI medium supplemented or not with filter-sterilized S. mutans culture supernatants. These analyses showed significant S. mitis binding to EPS and biofilm formation in the presence of S. mutans supernatants supplemented with sucrose, compared to BHI or BHI-sucrose medium. In addition, these phenotypes were abolished if strains were grown in culture supernatants of a gtfBCD-defective S. mutans mutant. Importantly, GtfB/C/D-associated phenotypes were enhanced in high PcsB-expressing strains, compared to low PcsB producers. Increased PcsB expression was further correlated with increased resistance to deposition of C3b/iC3b of the complement system after exposure to human serum, when strains were previously grown in the presence of S. mutans supernatants. Finally, analyses of PcsB polymorphisms and bioinformatic prediction of epitopes with significant binding to MHC class II alleles revealed that blood isolates harbor PcsB polymorphisms in its functionally conserved CHAP-domain, suggesting antigenic variation. These findings reveal important roles of PcsB in S. mitis-host interactions under commensal and pathogenic states, highlighting the need for studies to elucidate mechanisms regulating PcsB expression in this species. (AU)

• Processo FAPESP: 17/19899-4 - Identificação de fatores que modulam a susceptibilidade de Streptococcus sanguinis à imunidade mediada pelo sistema complemento
• Beneficiário: Lívia Araújo Alves
• Linha de fomento: Bolsas no Brasil - Pós-Doutorado
• 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
• Linha de fomento: 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
• Linha de fomento: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/02054-4 - Identificação de fatores que modulam a susceptibilidade de Streptococcus sanguinis à imunidade mediada pelo sistema complemento
• Beneficiário: Renata de Oliveira Mattos Graner
• Linha de fomento: 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
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 09/50547-0 - Characterization of GbpB/PcsB homologues in commensal species of oral streptococci
• Beneficiário: Erika Nikitza Shiauha Harth Chu
• Linha de fomento: 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
• Linha de fomento: Auxílio à Pesquisa - Regular