An Ecological Understanding of Quorum Sensing-Controlled Bacteriocin Synthesis

Bacteriocins are common antimicrobial agents that bacteria secrete to suppress the growth of competitors. Their production is often conditional, governed by underlying quorum sensing regulatory circuitry. Although the molecular underpinnings of controlled bacteriocin synthesis have been increasingly revealed, its quantitative ecological role has not been well characterized. Here, we present an integrated model of bacteriocin synthesis in the context of two-species contests where one species opposes the other for resource utilization. In a well-mixed environment, we find that bacteriocin production can contribute positively or negatively to the outcome of species competition, determined by the tradeoff between the benefit of bacteriocins in mediating competition and the fitness cost due to metabolic load. The tradeoff also determines the relative advantage between constitutive bacteriocin production and quorum sensing (QS) controlled production. Interestingly, under the naturally occurring scenario where bacteriocin production has a high cost, QS controlled synthesis outperforms constitutive, which offers a quantitative interpretation for the wide prevalence of density-related bacteriocin production in nature. Furthermore, by extending our study to include spatial dynamics of competing communities, we show that our finding, the superiority of QS controlled synthesis in the high cost regime, remains valid for complex settings. This work provides ecological insights into bacteriocin synthesis by revealing its cost and benefit during population growth, advancing our fundamental understanding of bacteriocin-mediated community organization as well as microbial ecology in general.

[1]  Y. Michel-Briand,et al.  The pyocins of Pseudomonas aeruginosa. , 2002, Biochimie.

[2]  Lejeune,et al.  Modelling the growth and bacteriocin production by Lactobacillus amylovorus DCE 471 in batch cultivation , 1998 .

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

[4]  Diarmaid Hughes,et al.  Antibiotic resistance and its cost: is it possible to reverse resistance? , 2010, Nature Reviews Microbiology.

[5]  W. Shi,et al.  LuxS controls bacteriocin production in Streptococcus mutans through a novel regulatory component , 2005, Molecular microbiology.

[6]  R. Lenski,et al.  Chemical warfare from an ecological perspective , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[7]  C. Hill,et al.  Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118 , 2007, Proceedings of the National Academy of Sciences.

[8]  H. Abriouel,et al.  Bacteriocin-based strategies for food biopreservation. , 2007, International journal of food microbiology.

[9]  Mario Mulansky,et al.  Odeint - Solving ordinary differential equations in C++ , 2011, ArXiv.

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

[11]  S. Rebuffat,et al.  Prokaryotic antimicrobial peptides , 2011 .

[12]  P. Courvalin,et al.  Fitness Cost of VanA-Type Vancomycin Resistance in Methicillin-Resistant Staphylococcus aureus , 2009, Antimicrobial Agents and Chemotherapy.

[13]  S. Schuster,et al.  Continuous model for the rock–scissors–paper game between bacteriocin producing bacteria , 2007, Journal of mathematical biology.

[14]  A. Driessen,et al.  Bacteriocins: mechanism of membrane insertion and pore formation , 1999, Antonie van Leeuwenhoek.

[15]  Wentao Kong,et al.  Cloning and optimization of a nisin biosynthesis pathway for bacteriocin harvest. , 2014, ACS synthetic biology.

[16]  D. Cavard Effects of temperature and of heat shock on the expression and action of the colicin A lysis protein , 1995, Journal of bacteriology.

[17]  M. Riley,et al.  A theoretical and empirical investigation of the invasion dynamics of colicinogeny. , 1999, Microbiology.

[18]  W. Crielaard,et al.  The VicRK System of Streptococcus mutans Responds to Oxidative Stress , 2007, Journal of dental research.

[19]  L. Vuyst,et al.  Bacteriocins of Lactic Acid Bacteria , 1994 .

[20]  V. Eijsink,et al.  Functional analysis of promoters involved in quorum sensing‐based regulation of bacteriocin production in Lactobacillus , 2000, Molecular microbiology.

[21]  R. Vogel,et al.  Mathematical evaluation of plantaricin formation supports an auto-induced production mechanism , 1999, Applied Microbiology and Biotechnology.

[22]  Andrew E. Blanchard,et al.  Slow and steady wins the race: a bacterial exploitative competition strategy in fluctuating environments. , 2015, ACS synthetic biology.

[23]  J. Tagg,et al.  Intra- and Interspecies Signaling betweenStreptococcus salivarius and Streptococcus pyogenes Mediated by SalA and SalA1 Lantibiotic Peptides , 2001, Journal of bacteriology.

[24]  W. Shi,et al.  Inactivation of the ciaH Gene in Streptococcus mutans Diminishes Mutacin Production and Competence Development, Alters Sucrose-Dependent Biofilm Formation, and Reduces Stress Tolerance , 2004, Infection and Immunity.

[25]  Ofer Levy,et al.  Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development , 2011, PloS one.

[26]  J. Vederas,et al.  Atypical Genetic Locus Associated with Constitutive Production of Enterocin B by Enterococcus faecium BFE 900 , 1999, Applied and Environmental Microbiology.

[27]  P. Garbeva,et al.  The Effect of Phylogenetically Different Bacteria on the Fitness of Pseudomonas fluorescens in Sand Microcosms , 2015, PloS one.

[28]  Nick C Fox,et al.  Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease , 2014, PLoS ONE.

[29]  S. Norris,et al.  Toxin Synthesis by Clostridium difficile Is Regulated through Quorum Signaling , 2015, mBio.

[30]  F. Blecha,et al.  Antimicrobial peptides and bacteriocins: alternatives to traditional antibiotics , 2008, Animal Health Research Reviews.

[31]  Daniel M. Cornforth,et al.  Competition sensing: the social side of bacterial stress responses , 2013, Nature Reviews Microbiology.

[32]  D. Hoover,et al.  Bacteriocins and their Food Applications. , 2003, Comprehensive reviews in food science and food safety.

[33]  Wentao Kong,et al.  A gene network engineering platform for lactic acid bacteria , 2015, Nucleic acids research.

[34]  C. Ghosh,et al.  Ribosomal Encoded Bacteriocins: Their Functional Insight and Applications , 2012 .

[35]  Benjamin Kerr,et al.  Competitive interactions in Escherichia coli populations: the role of bacteriocins , 2011, The ISME Journal.

[36]  J. Cleveland,et al.  Bacteriocins: safe, natural antimicrobials for food preservation. , 2001, International journal of food microbiology.

[37]  Erkang Wang,et al.  The Potential and Flux Landscape Theory of Ecology , 2014, PloS one.

[38]  Ting Lu,et al.  Population-Dynamic Modeling of Bacterial Horizontal Gene Transfer by Natural Transformation. , 2016, Biophysical journal.

[39]  M. Kleerebezem,et al.  Lactic acid bacteria - Genetics, metabolism and application. , 2005, FEMS microbiology reviews.

[40]  M. Kleerebezem Quorum sensing control of lantibiotic production; nisin and subtilin autoregulate their own biosynthesis , 2004, Peptides.

[41]  E. Smid,et al.  Natural Antimicrobials for Food Preservation , 2020, Handbook of Food Preservation.

[42]  Gabriele Bierbaum,et al.  The Lantibiotic Mersacidin Is an Autoinducing Peptide , 2006, Applied and Environmental Microbiology.

[43]  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.

[44]  Ting Lu,et al.  Bacterial social interactions drive the emergence of differential spatial colony structures , 2015, BMC Systems Biology.

[45]  Rolf F. Hoekstra,et al.  A spatial model of the evolution of quorum sensing regulating bacteriocin production , 2007 .

[46]  James D. Murray Mathematical Biology: I. An Introduction , 2007 .

[47]  Paul Waltman,et al.  A survey of mathematical models of competition with an inhibitor. , 2004, Mathematical biosciences.

[48]  R. P. Ross,et al.  Bacteriocins — a viable alternative to antibiotics? , 2012, Nature Reviews Microbiology.

[49]  J. V. D. Ploeg,et al.  Regulation of Bacteriocin Production in Streptococcus mutans by the Quorum-Sensing System Required for Development of Genetic Competence , 2005 .

[50]  K. Ochi,et al.  Guanine Nucleotides Guanosine 5′-Diphosphate 3′-Diphosphate and GTP Co-operatively Regulate the Production of an Antibiotic Bacilysin in Bacillus subtilis * , 2003, The Journal of Biological Chemistry.

[51]  W. Boer,et al.  Transcriptional and antagonistic responses of Pseudomonas fluorescens Pf0-1 to phylogenetically different bacterial competitors , 2011, The ISME Journal.

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

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

[54]  Y. Iwasa,et al.  Competition by allelopathy proceeds in traveling waves: colicin-immune strain aids colicin-sensitive strain. , 2000, Theoretical population biology.

[55]  The costs and benefits of killer toxin production by the yeast Pichia kluyveri , 2003, Antonie van Leeuwenhoek.

[56]  T. Abee Pore-forming bacteriocins of gram-positive bacteria and self-protection mechanisms of producer organisms. , 1995, FEMS microbiology letters.

[57]  W. D. de Vos,et al.  Autoregulation of Nisin Biosynthesis in Lactococcus lactis by Signal Transduction (*) , 1995, The Journal of Biological Chemistry.

[58]  G. Moore,et al.  Transcriptional Profiling of Colicin-Induced Cell Death of Escherichia coli MG1655 Identifies Potential Mechanisms by Which Bacteriocins Promote Bacterial Diversity , 2004, Journal of bacteriology.

[59]  C. Hill,et al.  Regulation of immunity to the two‐component lantibiotic, lacticin 3147, by the transcriptional repressor LtnR , 2001, Molecular microbiology.

[60]  Trine Nilsen,et al.  An Exported Inducer Peptide Regulates Bacteriocin Production in Enterococcus faecium CTC492 , 1998, Journal of bacteriology.

[61]  Qiang Hua,et al.  Programming the group behaviors of bacterial communities with synthetic cellular communication , 2014, Bioresources and Bioprocessing.

[62]  Erkang Wang,et al.  Potential Landscape and Probabilistic Flux of a Predator Prey Network , 2011, PloS one.

[63]  J. González-Pastor,et al.  The regulation of microcin B, C and J operons. , 2002, Biochimie.

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

[65]  R. P. Ross,et al.  Food microbiology: Bacteriocins: developing innate immunity for food , 2005, Nature Reviews Microbiology.

[66]  C. Lively,et al.  Bacteriocin-mediated interactions within and between coexisting species , 2012, Ecology and evolution.

[67]  F. Leroy,et al.  A Combined Model To Predict the Functionality of the Bacteriocin-Producing Lactobacillus sakei Strain CTC 494 , 2003, Applied and Environmental Microbiology.

[68]  Levin,et al.  Allelopathy in Spatially Distributed Populations , 1997, Journal of theoretical biology.

[69]  Jeff Hasty,et al.  Phenotypic variability of growing cellular populations , 2007, Proceedings of the National Academy of Sciences.

[70]  V. Eijsink,et al.  Induction of bacteriocin production in Lactobacillus sake by a secreted peptide , 1996, Journal of bacteriology.