Diversity of predicted regulatory sequences of swan, nox and spxB among S. sanguinis strains.

• Grant number: 25/09154-8
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: September 08, 2025
• End date: January 07, 2026
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Renata de Oliveira Mattos Graner
• Grantee: Emanoeli Daniel Bessa
• Supervisor: Tsute Chen
• Host Institution: Faculdade de Odontologia de Piracicaba (FOP). Universidade Estadual de Campinas (UNICAMP). Piracicaba , SP, Brazil
• Institution abroad: Forsyth Institute, United States
• Associated to the scholarship: 23/16788-8 - Analysis of the effects of the Streptococcus sanguinis genes spxB, swan and nox in NET production by human neutrophils, BP.IC

Abstract

Streptococcus sanguinis is a commensal bacterium of the oral cavity frequently associated withinfective endocarditis (IE) and atherosclerosis. This species has particular ability to persist in the bloodstream to, eventually, infect cardiovascular tissues. No specific set of virulence genes has been detected in strains associated with cardiovascular infection as compared to commensal oral strains. On the other hand, S. sanguinis strains seems to rely on the expression of swan, nox, and spxB to evade blood immunity mediated by the complement system and neutrophils (PMN). The mechanisms controlling the activities of these genes remains, however, to be addressed. The genome of the reference strain SK36 harbors genes encoding fourteen transcriptional regulatory systems of two-component (TCS), which are key systems modulating bacterial transcriptomes in response to environmental stimuli. Few of these TCS were investigate so far, and their roles on the regulation of swan, nox, and spxB transcription remains to be investigated. The aim of this project is to apply in silico analysis of the regulatory regions of swan, nox, and spxB in strains of S. sanguinis to identity their potential regulators. Bioinformatics and deep learning tools (recurrent neural network tool "ORAKLE"), will be applied for predicting the regulation of swan, nox, and spxB genes by different TCS. The conservation of the regulatory regions identified will be then assessed by identification of conserved binding motifs of specific TCS regulators and by multiple sequence alignment of the promoter regions of swan, nox and spxB. The findings of this study might shad light to the mechanisms regulating the expression of these virulence genes and thus, on the mechanisms underlying different behaviors of S. sanguinis as commensal or pathogens.