SummaryThe induction of genetic competence is a strategy used by bacteria to increase their genetic repertoire under stressful environmental conditions. Recently, Streptococcus pneumoniae has been shown to co-ordinate the uptake of transforming DNA with fratricide via increased expression of the peptide pheromone responsible for competence induction. Here, we document that environmental stress-induced expression of the peptide pheromone competencestimulating peptide (CSP) in the oral pathogen Streptococcus mutans. We showed that CSP is involved in the stress response and determined the CSP-induced regulon in S. mutans by microarray analysis. Contrary to pneumococcus, S. mutans responds to increased concentrations of CSP by cell lysis in only a fraction of the population. We have focused on the mechanism of cell lysis and have identified a novel bacteriocin as the 'death effector'. Most importantly, we showed that this bacteriocin causes cell death via a novel mechanism of action: intracellular action against self. We have also identified the cognate bacteriocin immunity protein, which resides in a separate unlinked genetic locus to allow its differential regulation. The role of the lytic response in S. mutans competence is also discussed. Together, these findings reveal a novel autolytic pathway in S. mutans which may be involved in the dissemination of fitness-enhancing genes in the oral biofilm.

Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental “resistome” is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity), while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-encoded β-lactamases). The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone resistance gene qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance.

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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.

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Background People with diabetes are at risk for diabetic foot ulcers (DFUs), which can lead to limb loss and a significant decrease in quality of life. Evidence suggests that mHealth can be an effective tool in diabetes self-management. mHealth presents an opportunity for the prevention and monitoring of DFUs. However, there is a paucity of research that explores its effectiveness in the DFU patient population, as well as the views and attitudes of these patients toward technology and mHealth. Objective This study aimed to explore the views, attitudes, and experiences of a diabetic patient population with or at risk of DFUs regarding technology, mHealth, and the diabetic foot. Methods We used a qualitative research approach using in-depth interviews with 8 patients with DFUs. Questions were structured around experience with technology, current health practices related to diabetic foot care, and thoughts on using an mHealth device that prevents and monitors DFUs. We transcribed and thematically analyzed all interviews. Results All patients had positive responses for an mHealth intervention aimed at preventing and monitoring DFUs. We found 4 themes in the data: diversity in use of technology, feet-checking habits, 2-way communication with health care professionals (HCPs), and functionality. There were varying levels of familiarity with and dependence on technology within this patient population. These relationships correlated with distinct generations found in North America, including baby boomers and Generation X. Furthermore, we found that most patients performed daily feet checks to monitor any changes in health. However, some did not perform feet checks prior to the development of a DFU. Patients expressed interest in 2-way communication with HCPs that would allow for easier appointment scheduling, sharing of medical data, decreased number of visits, and use of alerts for when medical attention is required. Patients also identified conditions of functionality for the mHealth intervention. These included consideration of debilitating complications because of diabetes, such as retinopathy and decreased mobility; ease of use of the intervention; and implementation of virtual communities to support continued use of the intervention. Conclusions Our patient population expressed an interest in mHealth for preventing and monitoring DFUs, although some participants were not frequent users of technology. mHealth continues to show potential in improving patient outcomes, and this study provides a foundation for designing interventions specific to a DFU population. Further research is needed to confirm these findings.

Aim:  To assess potential function of each two‐component signal transduction system in the expression of Streptococcus mutans virulence properties. Methods and Results:  For each two‐component system (TCS), the histidine kinase‐encoding gene was inactivated by a polymerase chain reaction (PCR)‐based deletion strategy and the effects of gene disruption on the cell’s ability to form biofilms, become competent, and tolerate acid, osmotic, and oxidative stress conditions were tested. Our results demonstrated that none of the mutations were lethal for S. mutans. The TCS‐2 (CiaRH) is involved in biofilm formation and tolerance to environmental stresses, the TCS‐3 (ScnRK‐like) participates in the survival of cells at acidic pH, and the TCS‐9 affects the acid tolerance response and the process of streptococcal competence development. Conclusions:  Our results confirmed the physiological role of the TCS in S. mutans cellular function, in particular the SncRK‐like TCS and TCS‐9 as they may represent new regulatory systems than can be involved in S. mutans pathogenesis. Significance and Impact of the Study:  Multiple TCS govern important biological parameters of S. mutans enabling its survival and persistence in the biofilm community.