Microarray-Based Identification of a NovelStreptococcus pneumoniae Regulon Controlled by an Autoinduced Peptide

ABSTRACT We have identified in the Streptococcus pneumoniaegenome sequence a two-component system (TCS13, Blp [bacteriocin-like peptide]) which is closely related to quorum-sensing systems regulating cell density-dependent phenotypes such as the development of genetic competence or the production of antimicrobial peptides in lactic acid bacteria. In this study we present evidence that TCS13 is a peptide-sensing system that controls a regulon including genes encoding Blps. Downstream of the Blp TCS (BlpH R) we identified open reading frames (blpAB) that have the potential to encode an ABC transporter that is homologous to the ComA/B export system for the competence-stimulating peptide ComC. The putative translation product of blpC, a small gene located downstream ofblpAB, has a leader peptide with a Gly-Gly motif. This leader peptide is typical of precursors processed by this family of transporters. Microarray-based expression profiling showed that a synthetic oligopeptide corresponding to the processed form of BlpC (BlpC*) induces a distinct set of 16 genes. The changes in the expression profile elicited by synthetic BlpC* depend on BlpH since insertional inactivation of its corresponding gene abolishes differential gene induction. Comparison of the promoter regions of theblp genes disclosed a conserved sequence element formed by two imperfect direct repeats upstream of extended −10 promoter elements. We propose that BlpH is the sensor for BlpC* and the conserved sequence element is a recognition sequence for the BlpR response regulator.

[1]  Hybridization analysis of labeled RNA by oligonucleotide arrays. , 2001, Methods in molecular biology.

[2]  James R. Brown,et al.  A genomic analysis of two‐component signal transduction in Streptococcus pneumoniae , 2000, Molecular microbiology.

[3]  P. Caspers,et al.  Domain organization and molecular characterization of 13 two-component systems identified by genome sequencing of Streptococcus pneumoniae. , 1999, Gene.

[4]  L. Håvarstein,et al.  Identification of DNA binding sites for ComE, a key regulator of natural competence in Streptococcus pneumoniae , 1999, Molecular microbiology.

[5]  Gary M. Dunny,et al.  Cell-cell signaling in bacteria , 1999 .

[6]  D. Diep,et al.  Identification of the DNA-binding sites for two response regulators involved in control of bacteriocin synthesis in Lactobacillus plantarum C11 , 1998, Molecular and General Genetics MGG.

[7]  A. Grossman,et al.  The ins and outs of peptide signaling. , 1998, Trends in microbiology.

[8]  Araceli M. Huerta,et al.  From specific gene regulation to genomic networks: a global analysis of transcriptional regulation in Escherichia coli. , 1998, BioEssays : news and reviews in molecular, cellular and developmental biology.

[9]  F. Vandenesch,et al.  Transmembrane topology and histidine protein kinase activity of AgrC, the agr signal receptor in Staphylococcus aureus , 1998, Molecular microbiology.

[10]  J. Claverys,et al.  Competence‐specific induction of recA is required for full recombination proficiency during transformation in Streptococcus pneumoniae , 1998, Molecular microbiology.

[11]  Antoine de Saizieu,et al.  Bacterial transcript imaging by hybridization of total RNA to oligonucleotide arrays , 1998, Nature Biotechnology.

[12]  M. Riley,et al.  Molecular mechanisms of bacteriocin evolution. , 1998, Annual review of genetics.

[13]  L. Wodicka,et al.  Genome-wide expression monitoring in Saccharomyces cerevisiae , 1997, Nature Biotechnology.

[14]  R. Hakenbeck,et al.  Natural competence in the genus Streptococcus: evidence that streptococci can change pherotype by interspecies recombinational exchanges , 1997, Journal of bacteriology.

[15]  V. Eijsink,et al.  Pheromone‐induced production of antimicrobial peptides in Lactobacillus , 1997, Molecular microbiology.

[16]  R. Beavis,et al.  Bacterial interference caused by autoinducing peptide variants. , 1997, Science.

[17]  A. Grossman,et al.  An Exported Peptide Functions Intracellularly to Contribute to Cell Density Signaling in B. subtilis , 1997, Cell.

[18]  Michiel Kleerebezem,et al.  Quorum sensing by peptide pheromones and two‐component signal‐transduction systems in Gram‐positive bacteria , 1997, Molecular microbiology.

[19]  B. Poolman,et al.  Thermophilin 13, a Nontypical Antilisterial Poration Complex Bacteriocin, That Functions without a Receptor* , 1997, The Journal of Biological Chemistry.

[20]  J. García,et al.  Identification and characterization of IS1381, a new insertion sequence in Streptococcus pneumoniae , 1997, Journal of bacteriology.

[21]  P. Andrew,et al.  Streptococcus pneumoniae produces a second haemolysin that is distinct from pneumolysin. , 1997, Microbial pathogenesis.

[22]  G. Dunny,et al.  Cell-cell communication in gram-positive bacteria. , 1997, Annual review of microbiology.

[23]  D. Diep,et al.  Characterization of the locus responsible for the bacteriocin production in Lactobacillus plantarum C11 , 1996, Journal of bacteriology.

[24]  D. Morrison,et al.  Regulation of competence for genetic transformation in Streptococcus pneumoniae by an auto‐induced peptide pheromone and a two‐component regulatory system , 1996, Molecular microbiology.

[25]  D. Lockhart,et al.  Expression monitoring by hybridization to high-density oligonucleotide arrays , 1996, Nature Biotechnology.

[26]  R. Beavis,et al.  Cell density control of staphylococcal virulence mediated by an octapeptide pheromone. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[27]  D. Morrison,et al.  An unmodified heptadecapeptide pheromone induces competence for genetic transformation in Streptococcus pneumoniae. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[28]  S. Lacks,et al.  An extended -10 promoter alone directs transcription of the DpnII operon of Streptococcus pneumoniae. , 1995, Journal of molecular biology.

[29]  M. Løvik,et al.  Virulence of Streptococcus pneumoniae in mice: a standardized method for preparation and frozen storage of the experimental bacterial inoculum. , 1995, Microbial pathogenesis.

[30]  M. Gilmore,et al.  Genetic structure of the Enterococcus faecalis plasmid pAD1-encoded cytolytic toxin system and its relationship to lantibiotic determinants , 1994, Journal of bacteriology.

[31]  E. Greenberg,et al.  Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators , 1994, Journal of bacteriology.

[32]  M. Zervos,et al.  Plasmid-associated hemolysin and aggregation substance production contribute to virulence in experimental enterococcal endocarditis , 1993, Antimicrobial Agents and Chemotherapy.

[33]  D. T. Elmore,et al.  Solid‐phase peptide synthesis: a practical approach , 1990 .

[34]  D. Morrison,et al.  Construction and properties of a new insertion vector, pJDC9, that is protected by transcriptional terminators and useful for cloning of DNA from Streptococcus pneumoniae. , 1988, Gene.

[35]  M. Smith,et al.  A plasmid in Streptococcus pneumoniae , 1979, Journal of bacteriology.

[36]  O. Avery,et al.  STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES , 1944, The Journal of experimental medicine.

[37]  L. Mindich Bacteriocins of Diplococcus pneumoniae I. Antagonistic Relationships and Genetic Transformations , 1966, Journal of bacteriology.

[38]  O. Avery,et al.  STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES , 1946, The Journal of experimental medicine.

[39]  O. Avery,et al.  STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES , 1946, The Journal of experimental medicine.