Inactivation ofStreptococcus mutansgeneslytSTanddltADimpairs its pathogenicityin vivo

Abstract

Background: Streptococcus mutans orchestrates the development of a biofilm that causes dental caries in the presence of dietary sucrose, and, in the bloodstream, S. mutans can cause systemic infections. The development of a cariogenic biofilm is dependent on the formation of an extracellular matrix rich in exopolysaccharides, which contains extracellular DNA (eDNA) and lipoteichoic acids (LTAs). While the exopolysaccharides are virulence markers, the involvement of genes linked to eDNA and LTAs metabolism in the pathogenicity of S. mutans remains unclear. Objective and Design: In this study, a parental strain S. mutans UA159 and derivative strains carrying single gene deletions were used to investigate the role of eDNA (ΔlytS and ΔlytT), LTA (ΔdltA and ΔdltD), and insoluble exopolysaccharides (ΔgtfB) in virulence in a rodent model of dental caries (rats) and a systemic infection model (Galleria mellonella larvae). Results: Fewer carious lesions were observed on smooth and sulcal surfaces of enamel and dentin of the rats infected with ΔlytS, ΔdltD, and ΔgtfB (vs. the parental strain). Moreover, strains carrying gene deletions prevented the killing of larvae (vs. the parental strain). Conclusions: Altogether, these findings indicate that inactivation of lytST and dltAD impaired S. mutans cariogenicity and virulence in vivo.

Modulation of Lipoteichoic Acids and Exopolysaccharides Prevents Streptococcus mutans Biofilm Accumulation

“…Although eDNA quantification showed statistically significant differences for the combination of myricetin, 1771 compound with or without fluoride, compared to the effect of treatments on EPS, myricetin and compound 1771 affected the amount of eDNA to a lesser extent (Figure 6). This matrix component is important in the construction, 3D architecture, and stability of the extracellular matrix [7,9], and the virulence of S. mutans biofilms [13]. Surprisingly, the expression of lrgA was higher in biofilms treated with the combination of Myr + 1771 + F and F alone; thus, this behavior may be associated with fluoride.…”

“…Approaches combining bioactive agents with fluoride for preventing cariogenic biofilm development have been proposed, including compounds that affect the production of an EPS-rich matrix [22,37]. Because EPS interacts with eDNA and LTA the extracellular matrix [9] and meddling with genes associated with EPS, eDNA and LTA reduces the cariogenicity of S. mutans [13], the current study investigated whether a compound that targets LTA metabolism in Gram-positive bacteria and works as an antimicrobial [23,24] would be effective for topical treatment and whether combining this agent with a flavonoid that hinders EPS production and fluoride would have a more pronounced effect in hampering S. mutans biofilm development.…”

“…Most of those genes have gene products involved with cell wall/membrane composition/structure, indicating that these cell components turnover may be affected, thereby influencing matrix and biofilm development [12]. The inactivation of lytST, dltAD, and gtfB impaired S. mutans cariogenicity in a rodent model, and its virulence in a systemic infection model (Galleria mellonella larvae) [13]. Hence, strategies to modulate these genes and their products could affect S. mutans pathogenicity.…”

Compounds with Distinct Targets Present Diverse Antimicrobial and Antibiofilm Efficacy against Candida albicans and Streptococcus mutans, and Combinations of Compounds Potentiate Their Effect

“…This compound inhibits the LTA synthesis [ 28 ], interfering with the cell wall composition, making the cytoplasmatic membrane an easy target for environmental stresses. Also, LTA from the cell wall are released in the matrix and interact with exopolysaccharides during the development and maturation of biofilms [ 41 ]; hence, interfering with LTA metabolism can impair cell wall and extracellular matrix composition. Thus, tt -farnesol and compound 1771 hindered S. mutans biofilms by promoting antimicrobial and antibiofilm activities.…”

Pengaruh Berkumur Dengan Larutan Teh Hijau dan Teh Hitam Terhadap pH Saliva

“…Penurunan nilai pH saliva dapat terjadi karena adanya proses metabolisme dari bakteri yang dapat menghasilkan asam dan dalam jangka waktu tertentu asam tersebut akan merusak lapisan email gigi sehingga menyebabkan gigi menjadi berlubang (10,11) . Salah satu bakteri yang dapat menghasilkan asam dan menjadi agen utama karies gigi adalah Streptococcus mutans (12) . pH saliva meningkat seiring dengan peningkatan sekresi saliva.…”