Cell death inStreptococcus mutans  biofilms: a link between CSP and extracellular DNA

Abstract

Streptococcal competence-stimulating peptides (CSPs) were once thought to passively communicate population density in a process known classically as quorum sensing. However, recent evidence has shown that these peptides may also be inducible ‘alarmones,’ capable of conveying sophisticated messages in a population including the induction of altruistic cellular suicide under stressful conditions. We have previously characterized the alarmone response in Streptococcus mutans, a cariogenic resident of the oral flora, in which a novel bacteriocin-like peptide causes cell death in a subset of the population. Our objective in this work was to characterize the mechanism of immunity to cell death in S. mutans. Toward this goal, we have identified the conditions under which immunity is induced, and identified the regulatory system responsible for differential (and protective) expression of immunity. We also showed that CSP-induced death contributes to S. mutans biofilm formation through the release of chromosomal DNA into the extracellular matrix, providing a long sought-after mechanistic explanation for the role of CSP in S. mutans biofilm formation.

Transcriptome analysis reveals that ClpXP proteolysis controls key virulence properties of Streptococcus mutans

“…For example, in addition to killing bacterial competitors, bacteriocin production has been linked to biofilm formation through extracellular DNA release and autolysis (Perry et al, 2009a, b). Perry et al (2009a) showed that intracellular accumulation of unprocessed CipB (mutacin V) mediates autolysis and proposed that CipB may be involved in altruistic cell death of a subset of the population (fratricide) during stressful conditions. It is tempting to speculate that the unexpected enhanced survival of DclpP and DclpX during acid stress (Kajfasz et al, 2009) could, at least partially, be explained by a reduction in normal levels of mutacin V-mediated autolysis in these strains.…”

Core Principles of Bacterial Autoinducer Systems

“…The demand might often be coupled with a willingness or ability to contribute. In a stressful situation, lower reproductive potential may favor altruistic behavior, which at its extreme may cause some cells to commit suicide to the benefit of others (131). From an efficiency point of view, all these factors affect the actual need of the bacterial cells for the regulated target behavior, their potential or willingness to contribute to it, or the opportunity for the regulated behavior to be effective.…”

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

“…Recent data has shown a drastic reduction of XIP levels in the comX (r x ) deficient S. mutans strains, as it evidence the positive feed-back role of ComX in ComRS/XIP expression where its binding sites were localized either within or upstream of ComRS [38]. Earlier reports have also demonstrated that the increase in the concentration (2-4 lM) of CSP mediated cell-killing and growth arrest of S. mutans [39,40]. Likewise, the S. mutans on exposure to 10 lM of synthetic XIP (sXIP) has shown the killing effect, naturally score the phenomena of exploiting the pheromones (XIP) as a potent effector molecules to treat dental caries [41].…”

“…The peptides were designed to have a targeted domain (8-aminoacid region of the CSP) fused with an antimicrobial peptide domain to show a robust species SigX (ComX) comR DNA transport, uptake and Recombination [12,36] ComAB nlmAB (comAB) Mutacin IV (bacteriocins), Maturation and export of CSP outside the cell [16,49] ComD comC/comD/comE (TCSTS) Class II bacteriocins and HK receptor for CSP signal [14,22] immA and immB (VicRK) comC Self-immunity proteins for protection from bacteriocins, acid tolerance [55] Lux S luxS Interspecies communication [39,40] Indian…”