VicRK and CovR polymorphisms in Streptococcus mutans strains associated with cardiovascular infections

Abstract

Introduction. Streptococcus mutans , a common species of the oral microbiome, expresses virulence genes promoting cariogenic dental biofilms, persistence in the bloodstream and cardiovascular infections. Gap statement. Virulence gene expression is variable among S. mutans strains and controlled by the transcription regulatory systems VicRK and CovR. Aim. This study investigates polymorphisms in the vicRK and covR loci in S. mutans strains isolated from the oral cavity or from the bloodstream, which were shown to differ in expression of covR, vicRK and downstream genes. Methodology. The transcriptional activities of covR, vicR and vicK were compared by RT-qPCR between blood and oral strains after exposure to human serum. PCR-amplified promoter and/or coding regions of covR and vicRK of 18 strains (11 oral and 7 blood) were sequenced and compared to the reference strain UA159. Results. Serum exposure significantly reduced covR and vicR/K transcript levels in most strains (P<0.05), but reductions were higher in oral than in blood strains. Single-nucleotide polymorphisms (SNPs) were detected in covR regulatory and coding regions, but SNPs affecting the CovR effector domain were only present in two blood strains. Although vicR was highly conserved, vicK showed several SNPs, and SNPs affecting VicK regions important for autokinase activity were found in three blood strains. Conclusions. This study reveals transcriptional and structural diversity in covR and vicR/K, and identifies polymorphisms of functional relevance in blood strains, indicating that covR and vicRK might be important loci for S. mutans adaptation to host selective pressures associated with virulence diversity.

Diversity in Phenotypes Associated With Host Persistence and Systemic Virulence in Streptococcus sanguinis Strains

“…Strain-specific genes associated with systemic virulence remains to be investigated in S. sanguinis strains ( Baker et al, 2018 ). Moreover, virulence capacity of streptococci further relies on the strain-specific upregulation of conserved virulence genes, apparently due to polymorphisms in transcription regulators of virulence ( Mattos-Graner and Duncan, 2017 ; Wilkening and Federle, 2017 ; Oliveira et al, 2021 ). In this study, we show that S. sanguinis strains largely differ in multiple phenotypes important for oral colonization and/or systemic virulence, such as biofilm formation, evasion to complement-mediated immunity, and invasion of primary HCAEC, clearly demonstrating that phenotypic observations on bacterial species need to be confirmed in multiple strains.…”

Estudos de fatores regulados por CovR e VicRK envolvidos na susceptibilidade à opsonização pelo sistema complemento e na virulência sistêmica de "Streptococcus mutans"

“…As razões da baixa expressão de covR nos isolados de sangue de S. mutans estão em estudo. Resultados preliminares revelam um grande número de mutações nas regiões promotoras de covR restritas a isolados de sangue(Oliveira et al, 2017).No capítulo II, investigamos as razões pelas quais a inativação do sistema VicRK inesperadamente aumenta a resistência de S. mutans à imunidade mediada pelo complemento. O principal papel do SDC VicRK na cariogenicidade de S. mutans está associado com a indução de79 genes requeridos para síntese (gtfB/C) e interação (gbpB) com PEC derivado da sacarose (Senadheera et al, 2005; Stipp et al, 2013).…”