Bacterial Cell-to-Cell Communication: Role in Virulence and Pathogenesis (Advances in Molecular and Cellular Microbiology, Series Number 11)

Considering the complexity of the topic covered in this book, it is incredibly readable. In short, it turns out that the view that bacterial cells are unaware of one another is quite wrong. They chatter away through the exchange of genetic amino acids. And they don't only communicate with their own species. They chat with a variety of species as they form biofilms, creating functional microbial societies where they feed off one another's secretions and defend one another against predators.90% of the cells in the human body are microbes. Most of them are quite friendly, but the few that are pathogenic can wreak havoc! Traditionally, antibiotics have been used to kill off unwanted bacteria, but that has resulted in more virulent strains that then resist drugs. So, this book proposes that we don't kill them, but simply knock out their cytoarchitectural communication infrastructures. That may sound militaristic, but if we can target the communication amino acids of only the virulent bacterias, then the human body could be more easily cured of disease while leaving the healthy microflora intact.As this book is so accessible, I would recommend it not just to scientists, but also anyone interested in this type of science and its metaphysical implications. Even if the chemistry is a bit much, the concepts are abundant and clear. The decriptions of viewing bacteria as collectives or biofilms versus individuals is compelling. This could easily lead to an overall reevaluation of what it means for a human to be a body. And it certainly suggests we reconsider just what our relationship to our own microflora is. Cover 1 Half-title 3 Series-title 5 Title 7 Copyright 8 Contents 9 Contributors 11 Preface 15 CHAPTER 1 Quorum sensing and regulation of Pseudomonas aeruginosa infections 19 Introduction 19 P.aeruginosa quorum sensing systems 20 Extending the P.aeruginosa QS realm 23 Influence of QS on P.aeruginosa virulence in plant and animal models 27 QS plays an active role in vivo 30 QS as a therapeutic target 31 References 33 CHAPTER 2 The Pseudomonas aeruginosa quinolone signal 41 Introduction 41 Discovery of PQS 41 Relationship of PQS to the P.aeruginosa quorum sensing circuitry 42 The genetics of PQS synthesis 43 The regulation of PQS synthesis 47 The timing of PQS production 49 PQS and P.aeruginosa virulence 51 The potential of PQS as a drug target 52 Other PQS-like molecules synthesized by P.aeruginosa 53 Concluding remarks 53 Acknowledgements 53 References 53 CHAPTER 3 Quorum-sensing-mediated regulation of plant–bacteria interactions and Agrobacterium tumefaciens virulence 57 Introduction 57 The Ti plasmids of A.tumefaciens and the discovery of AHLs as conjugal pheromones 58 Identification of a Ti-plasmid-encoded AHL synthase and AHL receptor 61 Regulation of traR expression 62 Post-transcriptional regulation of TraR activity 64 The role of OOHL in TraR maturation 67 Structure and function studies of TraR 68 TraR as an activator of transcription 71 Perspectives and future studies 73 Acknowledgements 75 References 76 CHAPTER 4 Jamming bacterial communications: new strategies to combat bacterial infections and the development of biofilms 83 Introduction 83 Why QS inhibitors? 84 Pseudomonas aeruginosa and QS 86 The involvement of QS in P.aeruginosa biofilm development 87 Natural blockers: a eukaryotic defense strategy against biofilms and biofouling 89 Synthetic analogs 91 Screens for QS inhibitors 94 Novel QSI screens 96 Novel natural QSIs 97 Transcriptomics: the ultimate tool for analyzing drug specificity 99 Biofilm models: what QSI drugs do to a biofilm 102 Pulmonary dose–response models 104 Treatment model 106 Antibiotics and QSI drugs: alone or together? 107 Acknowledgement 108 References 108 CHAPTER 5 Quorum-sensing-mediated regulation of biofilm growth and virulence of Vibrio cholerae 119 Introduction 119 Vibrio cholerae as a human pathogen and its infectious cycle 120 Quorum sensing regulation in V.cholerae 122 Quorum sensing negatively regulates virulence gene expression 124 Quorum sensing inhibits biofilm formation 125 Perspectives and future studies 129 Acknowledgements 130 References 131 CHAPTER 6 LuxS in cellular metabolism and cell-to-cell signaling 135 Introduction 135 Homoserine lactone quorum sensing systems 136 Oligopeptide quorum sensing pathways 136 Identification of LuxS 137 Metabolic pathway of AI-2 production 139 The structures of AI-2 141 The controversy of AI-2 and cell-to-cell signaling 144 AI-2 as a classical quorum sensing signal 146 AI-2 as a quorum sensing signal in bacteria other than Vibrio spp. 147 Bacteria with ambiguous roles for AI-2 150 AI-2 as an interspecies quorum sensing signal 152 Cell-to-cell signaling and AI-2 in dental plaque 153 The CF community 155 AI-2 as a reporter of metabolic status 156 Conclusions 159 References 160 CHAPTER 7 LuxS-dependent regulation of Escherichia coli virulence 169 Introduction 169 Enterohemorrhagic E.coli (EHEC) 169 LuxS and cell-to-cell signaling in bacteria 170 Cell-to-cell signaling in EHEC 173 Bacterial–host cell-to-cell signaling 175 The EHEC quorum-sensing signaling cascade 177 Quorum sensing in EPEC 184 Concluding remarks 185 References 186 CHAPTER 8 Quorum sensing and cell-to-cell communication in the dental biofilm 193 Introduction 193 Contact-dependent signaling in oral bacteria 194 Quorum-sensing-dependent communication among oral bacteria 198 Quorum sensing by autoinducer 2 in oral bacteria 200 Is AI-2 a quorum sensing signal in oral bacteria? 201 Physiologic role of LuxS-dependent signaling: regulation of iron acquisition 202 LuxS-dependent regulation of virulence and biofilm development 203 AI-2 signal transduction in A.actinomycetemcomitans and P. gingivalis 205 The A.actinomycetemcomitans AI-2 receptor 206 The A.actinomycetemcomitans AI-2 sensor kinase 208 AI-2 signal transduction in P.gingivalis 210 Crosstalk and implications for AI-2 signal specificity 210 Acknowledgements 212 References 212 CHAPTER 9 Quorum-sensing-dependent regulation of staphylococcal virulence and biofilm development 217 Introduction 217 The Agr quorum sensing system 218 Agr-regulated genes 221 Quorum sensing in other staphylococci 225 Staphylococcus epidermidis 225 Staphylococcus lugdunensis 226 Staphylococcus saprophyticus 227 Agr specificity groups 227 Agr regulation of virulence in the context of other regulators and the environment in vivo 229 SrrAB 230 The sae locus 230 ArlRS 231 The σB factor 231 ClpX and ClpP 231 The SarA family 232 Regulation by Agr in vivo 232 Agr and staphylococcal biofilms 234 Initial attachment 235 Maturation 235 Detachment 236 Agr variants and their role in staphylococcal pathogenesis 238 Inhibition of staphylococcal quorum sensing as a therapeutic tool 242 RIP/RAP 242 Conclusion 244 Acknowledgements 244 References 244 CHAPTER 10 Cell-density-dependent regulation of streptococcal competence 251 Introduction 251 A brief history 251 Cell-density-dependent competence development 253 Genetic competence regulation in S.pneumoniae 254 The ComCDE competence regulon in S.pneumoniae 254 The competence-stimulating peptide (CSP) 255 The ComD, CSP receptor 258 The ComE response regulator 259 ComX: the link to late competence genes 260 Competence-induced cell lysis 262 Competence shutoff 263 The CiaRH and VicRK two-component signal transduction systems (TCSTS) 264 The Blp quorum-sensing system 265 Genetic competence in oral streptococci 266 Transformation in Streptococcus gordonii 268 Genetics of competence development 268 Regulation of competence 269 Transformation in Streptococcus mutans 272 Genetic regulation of competence development 272 Study of competence in model biofilms 273 Other CSP-regulated phenotypes 276 Conclusions and future perspectives 277 References 278 CHAPTER 11 Signaling by a cell-surface-associated signal during fruiting-body morphogenesis in Myxococcus xanthus 287 Introduction 287 Multicellularity as a survival strategy 288 Gliding motility in M.xanthus 291 Intercellular signaling during fruiting-body morphogenesis 294 The C-signal induces three responses that are separated in time and space 295 The molecular nature of the C-signal 296 Synthesis of the C-signal 297 C-signal transmission relies on a contact-dependent mechanism 298 The C-signal transduction pathway 299 How does a single signal induce three responses separated in time and space? 303 Multiple signal transduction pathways control morphogenesis 305 The C-signal-dependent motility response 306 C-signal-induced aggregation: a model 307 Signal integration during fruiting-body morphogenesis 310 Concluding remarks 311 Acknowledgements 311 References 311 Index 319 Cover......Page 1 Half-title......Page 3 Series-title......Page 5 Title......Page 7 Copyright......Page 8 Contents......Page 9 Contributors......Page 11 Preface......Page 15 Introduction......Page 19 P.aeruginosa quorum sensing systems......Page 20 Extending the P.aeruginosa QS realm......Page 23 Influence of QS on P.aeruginosa virulence in plant and animal models......Page 27 QS plays an active role in vivo......Page 30 QS as a therapeutic target......Page 31 References......Page 33 Discovery of PQS......Page 41 Relationship of PQS to the P.aeruginosa quorum sensing circuitry......Page 42 The genetics of PQS synthesis......Page 43 The regulation of PQS synthesis......Page 47 The timing of PQS production......Page 49 PQS and P.aeruginosa virulence......Page 51 The potential of PQS as a drug target......Page 52 References......Page 53 Introduction......Page 57 The Ti plasmids of A.tumefaciens and the discovery of AHLs as conjugal pheromones......Page 58 Identification of a Ti-plasmid-encoded AHL synthase and AHL receptor......Page 61 Regulation of traR expression......Page 62 Post-transcriptional regulation of TraR activity......Page 64 The role of OOHL in TraR maturation......Page 67 Structure and function studies of TraR......Page 68 TraR as an activator of transcription......Page 71 Perspectives and future studies......Page 73 Acknowledgements......Page 75 References......Page 76 Introduction......Page 83 Why QS inhibitors?......Page 84 Pseudomonas aeruginosa and QS......Page 86 The involvement of QS in P.aeruginosa biofilm development......Page 87 Natural blockers: a eukaryotic defense strategy against biofilms and biofouling......Page 89 Synthetic analogs......Page 91 Screens for QS inhibitors......Page 94 Novel QSI screens......Page 96 Novel natural QSIs......Page 97 Transcriptomics: the ultimate tool for analyzing drug specificity......Page 99 Biofilm models: what QSI drugs do to a biofilm......Page 102 Pulmonary dose–response models......Page 104 Treatment model......Page 106 Antibiotics and QSI drugs: alone or together?......Page 107 References......Page 108 Introduction......Page 119 Vibrio cholerae as a human pathogen and its infectious cycle......Page 120 Quorum sensing regulation in V.cholerae......Page 122 Quorum sensing negatively regulates virulence gene expression......Page 124 Quorum sensing inhibits biofilm formation......Page 125 Perspectives and future studies......Page 129 Acknowledgements......Page 130 References......Page 131 Introduction......Page 135 Oligopeptide quorum sensing pathways......Page 136 Identification of LuxS......Page 137 Metabolic pathway of AI-2 production......Page 139 The structures of AI-2......Page 141 The controversy of AI-2 and cell-to-cell signaling......Page 144 AI-2 as a classical quorum sensing signal......Page 146 AI-2 as a quorum sensing signal in bacteria other than Vibrio spp.......Page 147 Bacteria with ambiguous roles for AI-2......Page 150 AI-2 as an interspecies quorum sensing signal......Page 152 Cell-to-cell signaling and AI-2 in dental plaque......Page 153 The CF community......Page 155 AI-2 as a reporter of metabolic status......Page 156 Conclusions......Page 159 References......Page 160 Enterohemorrhagic E.coli (EHEC)......Page 169 LuxS and cell-to-cell signaling in bacteria......Page 170 Cell-to-cell signaling in EHEC......Page 173 Bacterial–host cell-to-cell signaling......Page 175 The EHEC quorum-sensing signaling cascade......Page 177 Quorum sensing in EPEC......Page 184 Concluding remarks......Page 185 References......Page 186 Introduction......Page 193 Contact-dependent signaling in oral bacteria......Page 194 Quorum-sensing-dependent communication among oral bacteria......Page 198 Quorum sensing by autoinducer 2 in oral bacteria......Page 200 Is AI-2 a quorum sensing signal in oral bacteria?......Page 201 Physiologic role of LuxS-dependent signaling: regulation of iron acquisition......Page 202 LuxS-dependent regulation of virulence and biofilm development......Page 203 AI-2 signal transduction in A.actinomycetemcomitans and P. gingivalis......Page 205 The A.actinomycetemcomitans AI-2 receptor......Page 206 The A.actinomycetemcomitans AI-2 sensor kinase......Page 208 Crosstalk and implications for AI-2 signal specificity......Page 210 References......Page 212 Introduction......Page 217 The Agr quorum sensing system......Page 218 Agr-regulated genes......Page 221 Staphylococcus epidermidis......Page 225 Staphylococcus lugdunensis......Page 226 Agr specificity groups......Page 227 Agr regulation of virulence in the context of other regulators and the environment in vivo......Page 229 The sae locus......Page 230 ClpX and ClpP......Page 231 Regulation by Agr in vivo......Page 232 Agr and staphylococcal biofilms......Page 234 Maturation......Page 235 Detachment......Page 236 Agr variants and their role in staphylococcal pathogenesis......Page 238 RIP/RAP......Page 242 References......Page 244 A brief history......Page 251 Cell-density-dependent competence development......Page 253 The ComCDE competence regulon in S.pneumoniae......Page 254 The competence-stimulating peptide (CSP)......Page 255 The ComD, CSP receptor......Page 258 The ComE response regulator......Page 259 ComX: the link to late competence genes......Page 260 Competence-induced cell lysis......Page 262 Competence shutoff......Page 263 The CiaRH and VicRK two-component signal transduction systems (TCSTS)......Page 264 The Blp quorum-sensing system......Page 265 Genetic competence in oral streptococci......Page 266 Genetics of competence development......Page 268 Regulation of competence......Page 269 Genetic regulation of competence development......Page 272 Study of competence in model biofilms......Page 273 Other CSP-regulated phenotypes......Page 276 Conclusions and future perspectives......Page 277 References......Page 278 Introduction......Page 287 Multicellularity as a survival strategy......Page 288 Gliding motility in M.xanthus......Page 291 Intercellular signaling during fruiting-body morphogenesis......Page 294 The C-signal induces three responses that are separated in time and space......Page 295 The molecular nature of the C-signal......Page 296 Synthesis of the C-signal......Page 297 C-signal transmission relies on a contact-dependent mechanism......Page 298 The C-signal transduction pathway......Page 299 How does a single signal induce three responses separated in time and space?......Page 303 Multiple signal transduction pathways control morphogenesis......Page 305 The C-signal-dependent motility response......Page 306 C-signal-induced aggregation: a model......Page 307 Signal integration during fruiting-body morphogenesis......Page 310 References......Page 311 Index......Page 319 Many bacterial diseases are caused by organisms growing together as communities or biofilms. These microorganisms have the capacity to coordinately regulate specific sets of genes by sensing and communicating amongst themselves utilizing a variety of signals. This book examines the mechanisms of quorum sensing and cell-to-cell communication in bacteria and the roles that these processes play in regulating virulence, bacterial interactions with host tissues, and microbial development. Recent studies suggest that microbial cell-to-cell communication plays an important role in the pathogenesis of a variety of disease processes. Furthermore, some bacterial signal molecules may possess immunomodulatory activity. Thus, understanding the mechanisms and outcomes of bacterial cell-to-cell communication has important implications for appreciating host-pathogen interactions and ultimately may provide new targets for antimicrobial therapies that block or interfere with these communication networks.

Many bacterial diseases are caused by organisms growing together as communities or biofilms. These microorganisms have the capacity to coordinately regulate specific sets of genes by sensing and communicating amongst themselves utilizing a variety of signals. This book examines the mechanisms of quorum sensing and cell-to-cell communication in bacteria and the roles that these processes play in regulating virulence, bacterial interactions with host tissues, and microbial development. Recent studies suggest that microbial cell-to-cell communication plays an important role in the pathogenesis of a variety of disease processes.