title: Conserved mutations in the pneumococcal bacteriocin transporter gene, blpA, result in a complex population consisting of producers and cheaters.
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.
  
  
  OBJECTIVE
  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.
authors: Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, Michigan, USA.
authors: Matthew R
authors: MR
authors: Son
authors: Mikhail
authors: M
authors: Shchepetov
authors: Peter V
authors: PV
authors: Adrian
authors: Shabir A
authors: SA
authors: Madhi
authors: Linda
authors: L
authors: de Gouveia
authors: Anne
authors: A
authors: von Gottberg
authors: Keith P
authors: KP
authors: Klugman
authors: Jeffrey N
authors: JN
authors: Weiser
authors: Suzanne
authors: S
authors: Dawid
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001430:Bacteriocins / Q000378:metabolism*; D001483:Base Sequence; D016000:Cluster Analysis; D005260:Female; D016368:Frameshift Mutation; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010675:Pheromones / Q000378:metabolism; D010802:Phylogeny; D011008:Pneumococcal Infections / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D014774:Virulence
chemical_list: D018528:ATP-Binding Cassette Transporters; D001430:Bacteriocins; D010675:Pheromones