Coordinated Bacteriocin Expression and Competence in Streptococcus pneumoniae Contributes to Genetic Adaptation through Neighbor Predation

Abstract

Streptococcus pneumoniae (pneumococcus) has remained a persistent cause of invasive and mucosal disease in humans despite the widespread use of antibiotics and vaccines. The resilience of this organism is due to its capacity for adaptation through the uptake and incorporation of new genetic material from the surrounding microbial community. DNA uptake and recombination is controlled by a tightly regulated quorum sensing system that is triggered by the extracellular accumulation of competence stimulating peptide (CSP). In this study, we demonstrate that CSP can stimulate the production of a diverse array of blp bacteriocins. This cross stimulation occurs through increased production and secretion of the bacteriocin pheromone, BlpC, and requires a functional competence regulatory system. We show that a highly conserved motif in the promoter of the operon encoding BlpC and its transporter mediates the upregulation by CSP. The accumulation of BlpC following CSP stimulation results in augmented activation of the entire blp locus. Using biofilm-grown organisms as a model for competition and genetic exchange on the mucosal surface, we demonstrate that DNA exchange is enhanced by bacteriocin secretion suggesting that co-stimulation of bacteriocins with competence provides an adaptive advantage. The blp and com regulatory pathways are believed to have diverged and specialized in a remote ancestor of pneumococcus. Despite this, the two systems have maintained a regulatory connection that promotes competition and adaptation by targeting for lysis a wide array of potential competitors while simultaneously providing the means for incorporation of their DNA.

The blp Locus of Streptococcus pneumoniae Plays a Limited Role in the Selection of Strains That Can Cocolonize the Human Nasopharynx

“…On the other hand, they become at risk of elimination upon encountering a strain secreting a different BlpC type. Two recent publications (22,23) have demonstrated a regulatory connection between the com system, controlling competence, and the blp system. Those studies demonstrated that BlpC could be secreted by the ComAB competence-regulated transporter under competence-inducing conditions.…”

“…The link between the blp and com systems suggests that the blp locus could be important in increasing the DNA pool for transformation (22,23). Also, it could be important under specific conditions (e.g., nutrient limitation) or during the establishment of a strain during colonization by creating an isolated niche.…”

“…These systems were historically thought of as independent. However, recent work has demonstrated that they are coordinately regulated, suggesting that, under some circumstances, fratricide and bacteriocin production may work in concert to target neighboring cells (22,23).…”

“…BlpR activation results in upregulation of the entire blp locus (26), including the bacteriocin/immunity region (BIR) that encodes the bacteriocins and their cognate cotranscribed immunity proteins (27,28). Bacteriocins (and BlpC) are primarily secreted by the ABC transporter BlpAB (20)(21)(22)(23)26).…”

“…The prevalence of these strains suggests that strategies that limit locus stimulation and peptide secretion may provide an energetic advantage. It was recently shown that strains disrupted in blpAB can secrete a fraction of the blp pheromone, BlpC, through the activity of the homologous competence transporter, ComAB, allowing self-stimulation of the locus (22,23). This secretion occurs only during the competent state when sufficient ComAB is produced to support BlpC secretion and is enhanced by cross-stimulation of some of the blp promoters by the ComE competence response regulator.…”