| Title: | "Conserved mutations in the pneumococcal bacteriocin transporter gene, blpA, result in a complex population consisting of producers and cheaters" |
| Author(s): | Son MR; Shchepetov M; Adrian PV; Madhi SA; de Gouveia L; von Gottberg A; Klugman KP; Weiser JN; Dawid S; |
| Address: | "Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA" |
| Abstract: | "All fully sequenced strains of Streptococcus pneumoniae possess a version of the blp locus, which is responsible for bacteriocin production and immunity. Activation of the blp locus is stimulated by accumulation of the peptide pheromone, BlpC, following its secretion by the ABC transporter, BlpA. The blp locus is characterized by significant diversity in blpC type and in the region of the locus containing putative bacteriocin and immunity genes. In addition, the blpA gene can represent a single large open reading frame or be divided into several smaller fragments due to the presence of frameshift mutations. In this study, we use a collection of strains with blp-dependent inhibition and immunity to define the genetic changes that bring about phenotypic differences in bacteriocin production or immunity. We demonstrate that alterations in blpA, blpC, and bacteriocin/immunity content likely play an important role in competitive interactions between pneumococcal strains. Importantly, strains with a highly conserved frameshift mutation in blpA are unable to secrete bacteriocins or BlpC, but retain the ability to respond to exogenous peptide pheromone produced by cocolonizing strains, stimulating blp-mediated immunity. These 'cheater' strains can only coexist with bacteriocin-producing strains that secrete their cognate BlpC and share the same immunity proteins. The variable outcome of these interactions helps to explain the heterogeneity of the blp pheromone, bacteriocin, and immunity protein content. IMPORTANCE: Streptococcus pneumoniae resides in a polymicrobial environment and competes for limited resources by the elaboration of small antimicrobial peptides called bacteriocins. A conserved cluster of genes in the S. pneumoniae genome is involved in the production of bacteriocins and their associated protective immunity proteins through secretion of a signaling pheromone. In this study, we show that a significant number of strains have lost the ability to secrete bacteriocins and signaling pheromones due to a specific mutation in a dedicated transporter protein. Because the regulatory and immunity portion of the locus is retained, these 'cheater' strains can survive in the face of invasion from a bacteriocin-producing strain without the cost of bacteriocin secretion. The outcome of such interactions depends on each strain's repertoire of pheromone, immunity protein, and bacteriocin genes, such that intrastrain competition drives the diversity in bacteriocin, immunity protein, and pheromone content" |
| Keywords: | "ATP-Binding Cassette Transporters/*genetics/*metabolism Amino Acid Sequence Animals Bacteriocins/*metabolism Base Sequence Cluster Analysis Female *Frameshift Mutation *Genetic Variation Humans Mice Mice, Inbred BALB C Molecular Sequence Data Pheromones/m;" |
| Notes: | "MedlineSon, Matthew R Shchepetov, Mikhail Adrian, Peter V Madhi, Shabir A de Gouveia, Linda von Gottberg, Anne Klugman, Keith P Weiser, Jeffrey N Dawid, Suzanne eng K08 AI071090/AI/NIAID NIH HHS/ R01 AI078538/AI/NIAID NIH HHS/ K08AI071090/AI/NIAID NIH HHS/ R01AI078538/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2011/09/08 mBio. 2011 Sep 6; 2(5):e00179-11. doi: 10.1128/mBio.00179-11. Print 2011" |
