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

Author(s)

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]

Affiliation

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

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

• Document type: Journal article
• Source: FRONTIERS IN MICROBIOLOGY; v. 10, NOV 12 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 17/19899-4 - Identification of factors modulating the susceptibility of Streptococcus sanguinis to complement immunity
• Grantee: Lívia Araújo Alves
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/12940-3 - Identification of surface proteins of Streptococcus mutans involved in evasion of opsonization by the complement system
• Grantee: Renata de Oliveira Mattos Graner
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/04222-5 - Analysis of the roles of the transcriptional regulators VicRK and CovR in the susceptibility of Streptococcus mutans to opsonization by the complement system.
• Grantee: Lívia Araújo Alves
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/02054-4 - Identification of factors modulating the susceptibility of Streptococcus sanguinis to complement immunity
• Grantee: Renata de Oliveira Mattos Graner
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/07237-1 - Identification of surface proteins of Streptococcus mutans involved in the scape to opsonization by the complement system
• Grantee: Lívia Araújo Alves
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 09/50547-0 - Characterization of GbpB/PcsB homologues in commensal species of oral streptococci
• Grantee: Erika Nikitza Shiauha Harth Chu
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/50966-6 - Analysis of the roles of the transchptional regulators VicRK and CovR in the susceptibility of Streptococcus mutans and Streptococcus sanguinis to opsonization by the complement system
• Grantee: Renata de Oliveira Mattos Graner
• Support Opportunities: Regular Research Grants