Identification of G-quadruplex regions in the genomes of Streptococcus sanguinis strains isolated from oral and extra-oral sites

• Grant number: 24/00278-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2024
• End date: July 31, 2025
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Renata de Oliveira Mattos Graner
• Grantee: Felipe Romano Pires Lopes
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil

Abstract

Streptococcus sanguinis is an abundant commensal species of the oral cavity, which initiates tooth colonization, modulating the maturation of dental biofilms, and which can further promote opportunistic cardiovascular infections. These functions likely reflect the ability of S. sanguinis strains to adapt to oral and/or extra-oral environments, through the expression of a panel of signal transduction systems designated two-component systems (TCS). A TCS is formed by a sensor membrane protein (HK) which detects a specific signal and, through its kinase and/or phosphatase activities, activates a cognate intracellular response regulator (RR) for repressing or inducing target genes for appropriated bacterial responses to the sensed signal. There is evidence that expression of genes encoding particular TCS are modulated by G-quadruplex (G4) regions, which are noncanonical DNA secondary structures formed by guanine-rich sequences. Thus, the major aim of this project is to map through in silico analysis, the presence of G4 sequences associated with TCS gene loci identified in the genomes of S. sanguinis strains isolated from oral and extra-oral sites. To this end, fifteen TCS genes (identified in the reference strain SK36) will be scanned in the genomes of 72 S. sanguinis strains (retrieved from the GenBank and annotated using the PROKKA software). The annotated protein sequences will be then searched using BLASTP 2.13.0+ against all the TCS genes of the SK36 genome (GenBank; NC_009009.1).Then, G4-like sequences will be scanned through the bacterial genomes using the G4Hunter algorithm, and the predicted G4 loci will be mapped to identify G4 sequences associated with TCS genes. The number of putative G4 sequences identified for each TCS loci will be thenanalyzed per strain to assess the diversity in the profiles of G4 frequencies among strains and among different TCS. In addition, the profiles of TCS genes associated with potential G4 structures will be compared between strains isolated from the oral versus cardiovascular sites. This study might help to elucidate the genetic basis underlying differences in the expression of TCS associated with commensal and pathogenic lifestyles of S. sanguinis strains, thus providing clues for developing therapeutic approaches to prevent systemic infections by oral streptococci in susceptible subjects.