Microbial Endocrinology (eBook)

About the Editors 5
Preface 7
Contributors 10
Microbial Endocrinology: A Personal Journey 14
1.1 Introduction 14
1.2 From Psychoneuroimmunology to Microbial Endocrinology 15
1.2.1 Theoretical Reflections 15
1.2.2 Experimental Observations Leading to Microbial Endocrinology 17
1.2.3 Gaining Acceptance of Microbial Endocrinology 20
1.3 Collaboration and Dissemination 24
1.4 Whither Microbial Endocrinology 25
References 27
Evolutionary Considerations of Neurotransmitters in Microbial, Plant, and Animal Cells 30
2.1 Introduction 30
2.2 Occurrence of Neurotransmitters in Living Organisms 31
2.2.1 Discoveries 31
2.2.1.1 Acetylcholine 33
2.2.1.2 Catecholamines 34
2.2.1.3 Serotonin 35
2.2.1.4 Histamine 36
2.2.2 Neurotransmitters as Toxicants 37
2.2.3 Components of Cholinergic and Aminergic Systems 38
2.2.3.1 Choline Acetyltransferase 38
2.2.3.2 Cholinesterase 38
2.2.3.3 Enzymes of Biogenic Amine Metabolism 40
2.2.3.4 Recognition of Neurotransmitters 42
2.3 Common View on the Neurotransmitter (Biomediator) Functions 43
2.3.1 Functions of Neurotransmitters on Different Evolutionary Steps 43
2.3.1.1 Functions in Microorganisms 47
2.3.1.2 Function in Plants 49
2.3.1.3 Functions in Animals 50
2.3.1.4 Possible Evolution of Neurotransmitter Reception 51
2.3.2 Participation of Neurotransmitters in Chemical Relations Between Organisms 51
2.3.2.1 Microorganism–Microorganism Relations 51
2.3.2.2 Microorganism–Plant Relations 52
2.3.2.3 Microorganism–Animal Relations 52
2.3.2.4 Plant–Plant Relations 53
2.3.2.5 Plant–Animal Relations 53
2.3.2.6 Animal–Animal Relations 54
2.3.2.7 Biomediator Role of Neurotransmitters 54
2.4 Use of Microorganisms and Medicinal Plants Enriched in Neurotransmitters 55
2.4.1 Microbial Neurotransmitters 55
2.4.2 Plant Neurotransmitters 56
2.5 Conclusion 57
References 57
Mechanisms by Which Catecholamines Induce Growth in Gram-Negative and Gram-Positive Human Pathogens 66
3.1 Introduction: The Importance of Iron in Bacterial Growth 66
3.2 The Spectrum of Bacterial Catecholamine Growth Induction 67
3.3 Catecholamine-Transferrin and Lactoferrin Interactions 70
3.4 Bacterial Elements Involved in Catecholamine-Mediated Growth Induction 72
3.5 Catecholamines Induce Bacterial Growth via Production of Non-Homoserine Lactone Autoinducers 77
3.6 Iron Delivery May Not Be the Whole Story of Catecholamine-Mediated Growth Induction 78
3.7 Conclusion 79
References 80
Dietary Catechols and their Relationship to Microbial Endocrinology 82
4.1 Introduction 82
4.2 Dietary Sources and Distribution of Catechols 82
4.3 Dietary Intakes of Catechols 86
4.4 Absorption and Availability of Catechols 86
4.5 Bacterial Growth May be Stimulated Experimentally by a Range of Catechols 88
4.6 Are any of the Effects of Catechols on Bacteria Catecholamine-Specific? 90
4.7 Concluding Remarks 95
References 96
Interactions Between Bacteria and the Gut Mucosa: Do Enteric Neurotransmitters Acting on the Mucosal Epithelium Influence Intestinal Colonization or Infection? 101
5.1 Introduction 101
5.2 Gut Bacteria and Conversations Among Cells of the Intestinal Mucosa–Submucosa 102
5.2.1 Intestinal Epithelial Cells 102
5.2.2 Enteroendocrine Cells 102
5.2.3 Enteric Neurons 103
5.2.4 Diffuse and Organized Gut-Associated Lymphoid Tissue 103
5.3 The Enteric Nervous System, Mucosally Directed Nerves, and Gut Bacteria 105
5.3.1 Organization of the Enteric Nervous System 105
5.3.2 The ENS and Gut Bacteria 105
5.3.3 Catecholamines in the ENS 106
5.3.4 Catecholamine Receptor Pharmacology 107
5.3.5 Catecholamine Receptors and Mucosal Function 108
5.3.6 Enteric Nerves, Catecholamines, and IEC:Bacteria Interactions 109
5.3.6.1 Role of the ENS and Catecholamines in Bacterial Internalization into the Mucosa of the Small Intestine 110
5.3.6.2 Catecholamines and EHEC Adherence to the Mucosa of the Large Intestine 111
5.4 Other Biogenic Amines and Gut Bacteria 113
5.5 Conclusions 114
References 115
Modulation of the Interaction of Enteric Bacteria with Intestinal Mucosa by Stress-Related Catecholamines 122
6.1 Introduction 122
6.1.1 Stress and Enteric Bacterial Infections in Animals 122
6.1.2 Response of the Enteric Nervous System to Stress and Implications for Enteric Bacteria 123
6.2 Impact of Catecholamines on the Interaction of E. coli with Intestinal Mucosa 126
6.2.1 Possible Mechanisms of Action of Norepinephrine During E. coli Infection 128
6.3 Impact of Catecholamines on the Interaction of Salmonella with Intestinal Mucosa 134
6.3.1 Possible Mechanisms of Action of Norepinephrine During Salmonella Infection 135
6.4 Modulation of the Activities of Other Enteric Pathogens by Catecholamines 137
6.5 Concluding Remarks 138
References 139
The Role of Microbial Endocrinology in Periodontal Disease 146
7.1 Introduction to the Oral Cavity 146
7.2 What Is Periodontal Disease? 146
7.3 Stress Hormone Research in Periodontal Disease 148
7.4 Potential Implications of Stress Hormone Research Upon Periodontal Disease 149
7.5 Modification of Research Methodology of Anaerobes 150
7.6 Screening of Periodontal Bacteria for Responses to Norepinephrine and Epinephrine 151
7.7 Mechanisms of Catecholamine Responses by Periodontal Pathogens 154
7.8 Screening for Responses to Iron and Autoinducer 154
7.9 Host Iron-Binding Protein Experiments 155
7.10 Catecholamine Levels in the Oral Cavity 156
7.11 Future Areas of Research 158
References 159
Staphylococci, Catecholamine Inotropes and Hospital-Acquired Infections 162
8.1 Introduction: Nosocomial Infections 162
8.2 Historical Evidence Suggesting a Role for Microbial Endocrinology in Infectious Diseases of the Acutely Ill 163
8.3 Staphylococcal Infections in the ICU 165
8.4 Catecholamine Inotropes Induce Staphylococcal Growth and Biofilm Formation on Intravascular Catheters 166
8.5 Catecholamine Inotropes Can Resuscitate Antibiotic Damaged Staphylococci 168
8.6 Fighting Back: Blockade of Staphylococcal Catecholamine Responsiveness 171
8.7 Future Thoughts: Side Effects and Covert Side Effects 176
References 176
The Microbial Endocrinology of Pseudomonas aeruginosa 178
9.1 Epidemiology of Pseudomonas aeruginosa 178
9.2 Microbial Endocrinology of P. aeruginosa Virulence Activation in the Intestinal Tract Following Surgical Injury 179
9.3 Host Derived Bacterial Signaling Compounds (HDBSC’s): How Microbial Pathogens Sense Host Stress at the Intestinal Epithelial Surface 180
9.4 Mechanisms By Which Bacterial Membrane Proteins, Cytoplasmic Transcriptional Regulators, Microbial Enzymes, and Component of the Quorum Sensing Signaling System Gather, Process, and Transduce Host Compounds Released During Physiologic Sterss 181
9.4.1 Interferon-g 181
9.4.2 Adenosine/Inosine 182
9.4.3 Dynorphin 183
9.5 Phosphatonins and Phosphate Sensing by Pathogenic Bacteria: Microbial Endocrinology in Action 184
9.5.1 Pi Sensing by P. aeruginosa and Its Interaction with the QS System: A Conserved Mechanism of Virulence Activation in Nosocomical Pathogens 185
9.5.2 Modeling In Vivo Phosphate Depletion in the C. elegans–P. aeruginosa System: Discovery of “Red Death” 187
9.6 Summary and Conclusions 189
References 189
Mechanisms of Stress-Mediated Modulation of Upper and Lower Respiratory Tract Infections 191
10.1 Respiratory Immunity 191
10.2 Respiratory Mucosal Immunity, Neuronal Innervation, and Its Stress-Related Perturbations 192
10.3 Stress and Its Influence on Susceptibility to Respiratory Infection via Modulation of Respiratory Pathogen Growth and Virulence 195
10.4 Conclusion 196
References 197
Psychological Stress, Immunity, and the Effects on Indigenous Microflora 200
11.1 Introduction 200
11.2 Psychological Stress, the Stress Response, and the Impact on Immunity 201
11.3 Overview of the Indigenous Microflora 202
11.4 Stress-Induced Alterations in Intestinal Microflora 204
11.5 Prenatal Stressor-Induced Alterations to Microflora Development 207
11.6 Psychological Stress and the GI Tract: Toward a Mechanism of Stressor-Induced Alterations in Microflora 209
11.7 Stressor-Induced Bacterial Translocation 211
11.8 An Integrative Hypothesis of Stress, Infection, and Immunity 213
References 215
The Epinephrine/Norepinephrine/Autoinducer-3 Interkingdom Signaling System in Escherichia coli O157:H7 222
12.1 Escherichia coli O157:H7 222
12.2 Transcriptional Regulation of the LEE Region 225
12.3 Quorum Sensing in EHEC 226
12.4 Infectious Disease and Hormones 227
12.5 QseC: A Bacterial Functional Analog of an Adrenergic Receptor 228
12.6 QseBC Two-Component System 228
12.7 The QseEF Two-Component System 230
12.8 Qse A Regulator 230
12.9 Future Implications of the AI-3/Epinephrine/Norepinephrine InterKingdom Signaling in EHEC Pathogenesis and Development of Therapeutics 231
References 232
Molecular Profiling: Catecholamine Modulation of Gene Expression in Enteropathogenic Bacteria 237
13.1 Introduction 237
13.2 E. coli O157:H7 237
13.2.1 Conditions of O157:H7 Experiments 238
13.2.2 Shiga Toxin 238
13.2.3 Intimate Attachment 239
13.2.4 Motility, Curli, LPS, and Fimbriae 240
13.2.5 Iron Acquisition 240
13.2.6 Cold Shock Proteins 241
13.2.7 Positive Adaptive State 241
13.3 S. enterica serovar Typhimurium 242
13.3.1 Norepinephrine-Enhanced Motility 242
13.3.2 Norepinephrine-Enhanced Growth 243
13.3.3 Salmonella Pathogenicity Island 2 244
13.4 V. parahaemolyticus 245
13.5 Summary 245
References 246
Microbial Signaling Compounds as Endocrine Effectors 250
14.1 Contribution of Interkingdom Signaling to the Human Microbiome 250
14.2 Properties of an Interkingdom Signal 252
14.3 Candidate Interkingdom Signals 252
14.3.1 GABA: A Universal Signal? 253
14.3.1.1 Bacterial Production of GABA 253
14.3.1.2 GABA as an Interkingdom Signal 254
14.3.2 Insulin 255
14.3.3 Androgens and Glucocorticoids 255
14.3.4 Ovarian and Urogenital Hormones 256
14.3.5 Quorum Sensing Signals 257
14.3.5.1 Acyl Homoserine Lactones (AHLs) 257
14.3.5.2 Autoinducer-2 and Autoinducer-3 257
14.3.5.3 Autoinducing Peptides 258
14.3.5.4 Pseudomonas Quinolone Signal 259
14.3.5.5 Cyclic Diketopiperazines 259
14.3.5.6 Farnesol 259
14.3.6 Secondary Metabolites 263
14.3.6.1 Bacterial Secondary Metabolites as Interkingdom Signals 263
Pseudomonas Pyocyanin 263
Photorhabdus Stilbene 264
14.3.6.2 Fungal Secondary Metabolites/Mycotoxins 264
Aflatoxins 264
Zearalenone 265
Psilocybin 267
Ergotamine 267
14.4 Identifying Receptors for Interkingdom Signals 268
14.5 Concluding Remarks 269
References 269
Mycologic Endocrinology 276
15.1 Introduction 276
15.2 Hormones and Mating in Fungi 277
15.3 Interaction of Fungal Hormones with Plants, and Plant Hormones with Fungi 278
15.4 Interaction of Mammalian Hormones with Fungi 278
15.4.1 Hormone Influence on Growth of Fungi 279
15.5 Specific Steroid Binding Proteins in Fungi 279
15.5.1 Paracoccidioides brasiliensis 279
15.5.2 C. albicans 284
15.5.3 S. cerevisiae 286
15.5.4 Trichophyton and Microsporum 286
15.5.5 Coccidioides 287
15.5.6 Rhizopus nigricans 287
15.6 Functional Responses of Fungi to Hormones 288
15.6.1 C. albicans 288
15.6.2 S. cerevisiae 289
15.6.3 Aspergillus spp. 290
15.6.4 Cryptococcus 290
15.7 Effect of Hormonal Interactions on Antifungal Therapy 291
15.8 Future Directions 291
References 292
Experimental Design Considerations for In Vitro Microbial Endocrinology Investigations 298
16.1 Introduction 298
16.2 Choice of Growth Medium 300
16.3 Importance of Bacterial Inoculum Size 301
16.4 Choice of Neuroendocrine Hormone and Appropriate Concentration 305
16.5 Catecholamine-Induced Growth of Bacteria for Use in Animal Models 307
16.6 Analysis of Global Bacterial Gene Regulation by Catecholamines 308
16.7 Concluding Remarks 311
References 312
Index 316

"Chapter 9 The Microbial Endocrinology of Pseudomonas aeruginosa (p. 167-168)

John C. Alverdy, Kathleen Romanowski, Olga Zaborina, and Alexander Zaborin

9.1 Epidemiology of Pseudomonas aeruginosa

Pseudomonas aeruginosa is a model pathogen with which to advance the notion that microbial endocrinology plays a central role in the pathogenesis of bacteria and other microbes. P. aeruginosa is a gram-negative opportunistic pathogen that can infect a variety of host species, including Arabidopsis, Drosophila, Caenorhabditis elegans, rodents, and man.

Like many opportunistic pathogens, virulence expression in P. aeruginosa is not an invariant phenotype. Some investigators consider P. aeruginosa to be an accidental pathogen to man given that it does not appear to have co-evolved with the human immune system; as such it has been assumed to be rarely part of the normal commensal flora. Yet more comprehensive genome-based analyses of the human intestinal microflora suggest that P. aeruginosa is present in up to 20% of normal healthy individuals (Marshall 1991).

Although primarily considered to be a nosocomial pathogen that infects the injured and immunocompromised host, P. aeruginosa appears to be the most common cause of infection-related deaths among patients with cystic fibrosis, a genetic disorder of the respiratory epithelium. In this latter host, P. aeruginosa is a chronic colonizer that can persist for many years where it often exerts only moderate virulence.

In hospitalized patients, however, P. aeruginosa is most commonly isolated from the aero-digestive tract where it can colonize up to 50% of patients after as little as 3 days in hospital (Marshall 1991). Widespread and promiscuous use of antibiotics in the critically ill and injured appears to be among the various causes of the persistent prevalence of this pathogen in hospitalized patients. Attempts at predicting which colonizing pathogens are associated with the highest rates of virulence, and hence associated with the worst outcome has traditionally been assessed by genotyping and the use of antibiotic resistance profiles.

Even attempts at predicting outcome from patients who are infected versus colonized have yielded highly paradoxical results. In a recent study, patients with lung infection, i.e., pneumonia versus those with lung colonization (culture positive without pneumonia) demonstrated that the mortality rates were higher in colonized patients versus those that were clinically infected (Zhuo et al. 2008). Despite strict control measures, the prevalence and mortality rate of P. aeruginosa in hospitalized patients remain high and have not appreciably decreased in the last 10 years.

The highly opportunistic nature of P. aeruginosa, its ability to colonize and remain clinically elusive in antibiotic resistant biofilms, and its highly lethal virulence repertoire make this pathogen particularly difficult to detect and treat. The emergence of strains that are multi-drug resistant poses a real and present danger to patients who suffer burn injury, solid organ and bone marrow transplantation, traumatic injury, major surgical intervention, or severe immunocompromise such as HIV/AIDS.

Many of these infections arise from endogenous sources, the most common of which is the digestive tract reservoir. P. aeruginosa continues to carry the highest case fatality rate (60%) among nosocomial pathogens and is responsible for a variety of clinical infections, including keratitis, otitis, pneumonia, bacteremia, catheter-related sepsis, echthema gangrenosa, and severe diarrhea (Neuhauser et al. 2003)."