Plausible Drug Targets in the Streptococcus mutans Quorum Sensing Pathways to Combat Dental Biofilms and Associated Risks

Abstract

Streptococcus mutans, a Gram positive facultative anaerobe, is one among the approximately seven hundred bacterial species to exist in human buccal cavity and cause dental caries. Quorum sensing (QS) is a celldensity dependent communication process that respond to the inter/intra-species signals and elicit responses to show behavioral changes in the bacteria to an aggressive forms. In accordance to this phenomenon, the S. mutans also harbors a Competing Stimulating Peptide (CSP)-mediated quorum sensing, ComCDE (Two-component regulatory system) to regulate several virulence-associated traits that includes the formation of the oral biofilm (dental plaque), genetic competence and acidogenicity. The QS-mediated response of S. mutans adherence on tooth surface (dental plaque) imparts antibiotic resistance to the bacterium and further progresses to lead a chronic state, known as periodontitis. In recent years, the oral streptococci, S. mutans are not only recognized for its cariogenic potential but also well known to worsen the infective endocarditis due to its inherent ability to colonize and form biofilm on heart valves. The review significantly appreciate the increasing complexity of the CSP-mediated quorum-sensing pathway with a special emphasis to identify the plausible drug targets within the system for the development of anti-quorum drugs to control biofilm formation and associated risks.

Potential Emergence of Multi-quorum Sensing Inhibitor Resistant (MQSIR) Bacteria

“…Clostridium are noted to contain either single or multiple QSS, such as: (1) LuxS, (2) Agr, (3) Agr2 that are regulated by peptide signals e.g., AIP ( Table 1) [24][25][26][27][28][29]. Table 1) [30][31][32][33][34].…”

Multiplicity of Quorum Quenching Enzymes: A Potential Mechanism to Limit Quorum Sensing Bacterial Population

“…QS is a cell density dependent phenomenon, which operates through signal molecules. Above a threshold concentration, these signal molecules lead to the expression of selective genes, including those responsible for virulence [12,13]. QS systems (QSS) such as LuxI/R and their homologs range from a single in Vibrio species to multiple in Sinorhizobium and Pseudomonas species.…”

Analysis of multidrug resistance in Streptococcus suis ATCC 700794 under tylosin stress

“…Among them, the translation elongation Factor-G (EF-G) was reported to increase the resistance to kanamycin in E. coli via different point mutations in EF-G [24,45]. EF-Tu, another elongation factor, is the target of four families of antibiotics viz kirromycin, enacyloxin IIa, pulvomycin and GE2270A in E. coli [46,47]. Additionally, EF-G and EF-Tu have been identified as up-regulated proteins in tylosinresistant M. gallisepticum [27].…”

“…This sate is referred to as competence. Bacteria belonging to the Streptococcus genus, such as S. pneumoniae, Streptococcus mutans and S. suis are reported to be transformable species [46,52]. The TCS pathway, ComCDE, is involved in controlling competence.…”