Oscillations in continuous culture populations of Streptococcus pneumoniae: population dynamics and the evolution of clonal suicide

Agents that kill or induce suicide in the organisms that produce them or other individuals of the same genotype are intriguing puzzles for ecologists and evolutionary biologists. When those organisms are pathogenic bacteria, these suicidal toxins have the added appeal as candidates for the development of narrow spectrum antibiotics to kill the pathogens that produce them. We show that when clinical as well as laboratory strains of Streptococcus pneumoniae are maintained in continuous culture (chemostats), their densities oscillate by as much as five orders of magnitude with an apparently constant period. This dynamic, which is unanticipated for single clones of bacteria in chemostats, can be attributed to population-wide die-offs and recoveries. Using a combination of mathematical models and experiments with S. pneumoniae, we present evidence that these die-offs can be attributed to the autocatalytic production of a toxin that lyses or induces autolysis in members of the clone that produces it. This toxin, which our evidence indicates is a protein, appears to be novel; S. pneumoniae genetic constructs knocked out for lytA and other genes coding for known candidates for this agent oscillate in chemostat culture. Since this toxin lyses different strains of S. pneumoniae as well as other closely related species of Streptococcus, we propose that its ecological role is as an allelopathic agent. Using a mathematical model, we explore the conditions under which toxins that kill members of the same clone that produces them can prevent established populations from invasion by different strains of the same or other species. We postulate that the production of the toxin observed here as well as other bacteria-produced toxins that kill members of the same genotype, ‘clonal suicide’, evolved and are maintained to prevent colonization of established populations by different strains of the same and closely related species.

[1]  D. Maddison,et al.  Mesquite: a modular system for evolutionary analysis. Version 2.6 , 2009 .

[2]  T. Bereczkei,et al.  Facialmetric similarities mediate mate choice: sexual imprinting on opposite-sex parents , 2009, Proceedings of the Royal Society B: Biological Sciences.

[3]  V. Eldholm,et al.  A predatory mechanism dramatically increases the efficiency of lateral gene transfer in Streptococcus pneumoniae and related commensal species , 2008, Molecular microbiology.

[4]  Germán E. Piñas,et al.  Acidic stress induces autolysis by a CSP-independent ComE pathway in Streptococcus pneumoniae. , 2008, Microbiology.

[5]  Stephen P Ellner,et al.  Cryptic Population Dynamics: Rapid Evolution Masks Trophic Interactions , 2007, PLoS biology.

[6]  M. Nuhn,et al.  Diversity of Bacteriocins and Activity Spectrum in Streptococcus pneumoniae , 2007, Journal of bacteriology.

[7]  M. Nei,et al.  MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. , 2007, Molecular biology and evolution.

[8]  Ziheng Yang.  PAML 4: phylogenetic analysis by maximum likelihood. , 2007, Molecular biology and evolution.

[9]  M. Lipsitch,et al.  SpxB Is a Suicide Gene of Streptococcus pneumoniae and Confers a Selective Advantage in an In Vivo Competitive Colonization Model , 2007, Journal of bacteriology.

[10]  J. Claverys,et al.  Competence‐induced fratricide in streptococci , 2007, Molecular microbiology.

[11]  Jean-Pierre Claverys,et al.  Cannibalism and fratricide: mechanisms and raisons d'être , 2007, Nature Reviews Microbiology.

[12]  J. Weiser,et al.  The blp Bacteriocins of Streptococcus pneumoniae Mediate Intraspecies Competition both In Vitro and In Vivo , 2006, Infection and Immunity.

[13]  M. Lipsitch,et al.  Interference between Streptococcus pneumoniae and Staphylococcus aureus: In Vitro Hydrogen Peroxide-Mediated Killing by Streptococcus pneumoniae , 2006, Journal of bacteriology.

[14]  R. Losick,et al.  A Three-Protein Signaling Pathway Governing Immunity to a Bacterial Cannibalism Toxin , 2006, Cell.

[15]  J. Claverys,et al.  New insights into the pneumococcal fratricide: relationship to clumping and identification of a novel immunity factor , 2006, Molecular microbiology.

[16]  G. Pozzi,et al.  Sensor domain of histidine kinase ComD confers competence pherotype specificity in Streptoccoccus pneumoniae. , 2005, FEMS microbiology letters.

[17]  Sébastien Guiral,et al.  Competence-programmed predation of noncompetent cells in the human pathogen Streptococcus pneumoniae: genetic requirements. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[18]  P. Wiener.  Experimental studies on the ecological role of antibiotic production in bacteria , 1996, Evolutionary Ecology.

[19]  J. Claverys,et al.  Release of DNA into the medium by competent Streptococcus pneumoniae: kinetics, mechanism and stability of the liberated DNA , 2004, Molecular microbiology.

[20]  R. Fleischmann,et al.  Identification of competence pheromone responsive genes in Streptococcus pneumoniae by use of DNA microarrays , 2004, Molecular microbiology.

[21]  L. Håvarstein,et al.  Competence-Induced Cells of Streptococcuspneumoniae Lyse Competence-Deficient Cells of the SameStrain duringCocultivation , 2003, Journal of bacteriology.

[22]  John P. Huelsenbeck,et al.  MrBayes 3: Bayesian phylogenetic inference under mixed models , 2003, Bioinform..

[23]  R. Losick,et al.  Cannibalism by Sporulating Bacteria , 2003, Science.

[24]  D. Snydman,et al.  An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered, and clinical outcome. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[25]  J. Claverys,et al.  Extracellular-peptide control of competence for genetic transformation in Streptococcus pneumoniae. , 2002, Frontiers in bioscience : a journal and virtual library.

[26]  M. Feldman,et al.  Local dispersal promotes biodiversity in a real-life game of rock–paper–scissors , 2002, Nature.

[27]  L. Håvarstein,et al.  Induction of natural competence in Streptococcus pneumoniae triggers lysis and DNA release from a subfraction of the cell population , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[28]  J. Claverys,et al.  Identification of a Protein That Inactivates the Competence-Stimulating Peptide of Streptococcus pneumoniae , 2002, Journal of bacteriology.

[29]  T. Czárán,et al.  Chemical warfare between microbes promotes biodiversity , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[30]  M. Riley,et al.  Bacteriocins: evolution, ecology, and application. , 2002, Annual review of microbiology.

[31]  John P. Huelsenbeck,et al.  MRBAYES: Bayesian inference of phylogenetic trees , 2001, Bioinform..

[32]  K. Amrein,et al.  Microarray-Based Identification of a NovelStreptococcus pneumoniae Regulon Controlled by an Autoinduced Peptide , 2000, Journal of bacteriology.

[33]  K. Lewis,et al.  Programmed Death in Bacteria , 2000, Microbiology and Molecular Biology Reviews.

[34]  M. Riley,et al.  The ecological role of bacteriocins in bacterial competition. , 1999, Trends in microbiology.

[35]  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.

[36]  I. Nes,et al.  Identification of the streptococcal competence‐pheromone receptor , 1996, Molecular microbiology.

[37]  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.

[38]  B. Levin.  Frequency-dependent selection in bacterial populations. , 1988, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[39]  J. Sánchez-Puelles,et al.  Biological role of the pneumococcal amidase. Cloning of the lytA gene in Streptococcus pneumoniae. , 1987, European journal of biochemistry.

[40]  J. García,et al.  Searching for autolysin functions. Characterization of a pneumococcal mutant deleted in the lytA gene. , 1986, European journal of biochemistry.

[41]  L. Chao,et al.  Structured habitats and the evolution of anticompetitor toxins in bacteria. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[42]  B. Levin.  Periodic selection, infectious gene exchange and the genetic structure of E. coli populations. , 1981, Genetics.

[43]  F. M. Stewart,et al.  A Complex Community in a Simple Habitat: An Experimental Study with Bacteria and Phage , 1977 .

[44]  Bruce R. Levin,et al.  Partitioning of Resources and the Outcome of Interspecific Competition: A Model and Some General Considerations , 1973, The American Naturalist.

[45]  H. E. Kubitschek.  Introduction to research with continuous cultures , 1970 .

[46]  J. Monod.  The Growth of Bacterial Cultures , 1949 .

[47]  T.W.T. Dillon,et al.  What Is a Complex , 1943 .