An electrostatic interaction between BlpC and BlpH dictates pheromone specificity in the control of bacteriocin production and immunity in Streptococcus pneumoniae

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Abstract

The blp locus of Streptococcus pneumoniae secretes and regulates bacteriocins, which mediate both intra- and interspecific competition in the human nasopharynx. There are four major alleles of the gene blpH, which encodes the receptor responsible for activating the blp locus when bound to one of four distinct peptide pheromones (BlpC). The allelic variation of blpH is presumably explained by a need to restrict cross talk between competing strains. The BlpH protein sequences have polymorphisms distributed throughout the sequence, making identification of the peptide binding site difficult to predict. To identify the pheromone binding sites that dictate pheromone specificity, we have characterized the four major variants and two naturally occurring chimeric versions of blpH in which recombination events appear to have joined two distinct blpH alleles together. Using these allelic variants, a series of laboratory-generated chimeric blpH alleles, and site-directed mutants of both the receptor and peptide, we have demonstrated that BlpC binding to some BlpH types involves an electrostatic interaction between the oppositely charged residues of BlpC and the first transmembrane domain of BlpH. An additional recognition site was identified in the second extracellular loop. We identified naturally occurring BlpH types that have the capacity to respond to more than one BlpC type; however, this change in specificity results in a commensurate drop in overall sensitivity. These natural recombination events were presumably selected for to balance the need to sense bacteriocin-secreting neighbors with the need to turn on bacteriocin production at a low density.

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Pinchas, M. D., LaCross, N. C., & Dawid, S. (2015). An electrostatic interaction between BlpC and BlpH dictates pheromone specificity in the control of bacteriocin production and immunity in Streptococcus pneumoniae. Journal of Bacteriology, 197(7), 1236–1248. https://doi.org/10.1128/JB.02432-14

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