Bacterial Disease Mechanisms: An Introduction to Cellular Microbiology

by Michael Wilson , Rod McNab , Brian Henderson

• ISBN13: 9780521796897
• ISBN10: 052179689X
• Format: Paperback
• Copyright: 2002-05-13
• Publisher: Cambridge University Press

Summary

Antibiotic resistance and our consequent inability to treat many bacterial infections had fuelled an urgent need to understand the means by which bacteria cause disease. This has lead to a renaissance in research into bacterial disease mechanisms and the birth of a new discipline - cellular microbiology. The fruits of such research and how they have lead to an alternative perspective on bacteria-host interactions are described in this introductory textbook. The central premise is that bacteria have evolved means of manipulating normal host cell functions and overcoming host defence systems to ensure their survival. As well as offering an interesting perspective on the classical bacterial virulence mechanisms, this book outlines the molecular techniques developed to unravel the complexity of bacteria-host interactions. Research may lead not only to a better understanding of disease mechanisms, but also to alternative means of preventing and/or treating bacterial infections.

Table of Contents

Preface	xvii
Abbreviations used	xxi
An introduction to bacterial diseases	1	(45)
Introduction	1	(1)
The normal bacterial flora of humans	2	(14)
The skin	7	(2)
The oral cavity	9	(1)
The respiratory tract	10	(2)
The gastrointestinal tract	12	(3)
The urogenital tract	15	(1)
Bacteria and disease	16	(10)
Types of host-bacteria interaction	16	(2)
Diseases caused by members of the normal microflora	18	(2)
Damage to the epithelium	20	(1)
The presence of a foreign body	21	(1)
The transfer of bacteria to sites where they are not part of the normal microflora	21	(1)
Suppression of the immune system by drugs or radiation	22	(1)
Impairment of host defences due to infection by an exogenous pathogen	22	(1)
Disruption of the normal microflora by antibiotics	23	(1)
Unknown precipitating factor	23	(1)
Exogenous infections	24	(2)
The spectrum of bacterial diseases	26	(10)
Infections that are not usually accompanied by tissue invasion and Dissemination	28	(1)
Infections confined to mucosal surfaces	28	(3)
Infections confined to the skin	31	(2)
Infections accompanied by tissue invasion and dissemination	33	(1)
Causative organism produces an exotoxin	33	(1)
Causative organism does not produce an exotoxin	34	(2)
Concept check	36	(1)
Introduction to the paradigm organisms	37	(3)
Streptococcus pyogenes	37	(2)
Escherichia coli	39	(1)
What's next?	40	(1)
Questions	41	(1)
Further reading	42	(2)
Internet links	44	(2)
Bacterial cell biology	46	(65)
Introduction	46	(1)
Bacterial ultra structure	47	(10)
Size, shape and organisation	47	(2)
Cytoplasmic membrane	49	(1)
Cytoplasm	50	(1)
Bacterial cell wall	50	(1)
Gram-positive cell wall	51	(2)
Gram-negative cell wall	53	(1)
Cell wall of Mycobacterium spp.	54	(1)
Surface appendages	55	(1)
Cell-surface-associated components	56	(1)
Bacterial cell cycle	57	(2)
Sporulation	59	(2)
Bacterial protein secretion systems	61	(14)
The general secretory pathway	62	(2)
The Tat export pathway	64	(2)
Terminal branches of the GSP	66	(1)
The main terminal branch (type II secretion)	67	(2)
The chaperone-usher pathway	69	(1)
Type IV secretion	69	(1)
Type I secretion	70	(2)
Type III secretion	72	(3)
Genetic aspects of bacterial virulence	75	(21)
Gene regulation	76	(1)
Sensing changes in the environment	76	(1)
Gene transcription	77	(2)
Gene induction and repression	79	(3)
Antigenic and phase variation	82	(1)
DNA inversion	82	(2)
DNA recombination	84	(1)
Slipped-strand mispairing	85	(1)
Epigenetic variation	86	(1)
Point mutations	86	(1)
Mobile genetic elements	87	(1)
Plasmids	87	(1)
Bacteriophages	88	(1)
Transposable elements	89	(3)
Pathogenicity islands	92	(4)
Bacterial biofilms	96	(5)
Concept check	101	(1)
Cell biology of the paradigm organisms	102	(4)
Streptococcus pyogenes	102	(3)
Escherichia coli	105	(1)
What's next?	106	(1)
Questions	106	(1)
Further reading	107	(2)
Internet links	109	(2)
Molecular analysis of bacterial virulence mechanisms	111	(51)
Introduction	111	(2)
Mutational analysis	113	(8)
Directed mutagenesis	113	(3)
Random mutagenesis	116	(1)
Signature-tagged mutagenesis	117	(4)
Protein expression approaches	121	(9)
Surface and secreted proteins	121	(3)
Proteomics	124	(1)
Proteomic methodology	124	(5)
Proteomics in microbiology	129	(1)
Subtractive and differential analysis of mRNA	130	(4)
In vivo expression technology	134	(3)
Reporter systems	137	(4)
Genomic approaches	141	(3)
Assessing gene expression using DNA microarrays	144	(2)
Eukaryotic molecular methods	146	(11)
Yeast two-hybrid screening	146	(1)
Description of the technique	146	(2)
Use of the two-hybrid system in investigating bacterial virulence factors	148	(1)
Transgenesis and the generation of gene knockouts	149	(1)
Description of the technique	149	(2)
Knockout mice in bacterial virulence research	151	(2)
Dominant-negative mutants	153	(1)
Description of the technique	153	(2)
Use of dominant-negative mutants in the study of bacterial virulence	155	(1)
Oligonucleotide-based gene inactivation	156	(1)
Concept check	157	(1)
What's next?	157	(1)
Questions	158	(1)
Further reading	158	(3)
Internet links	161	(1)
Communication in infection	162	(76)
Introduction	162	(2)
Eukaryotic cell signalling	164	(45)
A brief overview of eukaryotic cell-cell signalling	164	(1)
Cell receptors for signal transduction	165	(1)
Ion channel receptors	166	(1)
G protein-coupled receptors (GPCR)	166	(3)
The GTPase superfamily	169	(1)
Receptors with inherent enzymic activity	170	(2)
Receptors linked to a separate cytoplasmic enzyme	172	(1)
Intracellular signal transduction	172	(2)
The basic building blocks of intracellular signal transduction	174	(8)
Signal transduction and selective gene transcription	182	(1)
The JAK/STAT pathway of gene activation	183	(1)
Gene transcription via the MAP kinase pathways	184	(4)
Signal transduction and the cell cytoskeleton	188	(1)
Integrins and cell signalling	189	(1)
Small GTPases and regulation of the actin cytoskeleton	189	(3)
Cyokines: key host signalling molecules	192	(1)
A brief history of cytokines	193	(1)
Properties of cytokines	194	(1)
Cytokine nomenclature	195	(1)
Biological actions of cytokines	195	(5)
Cytokine networks	200	(1)
Cytokine structure and cytokine receptors	201	(8)
Prokaryotic cell signalling	209	(16)
Intracellular signalling in prokaryotes	209	(1)
Introduction	209	(2)
Two-component signal transduction	211	(5)
Other signal transduction pathways in bacteria	216	(1)
Monitoring of the internal environment of the bacterium	216	(1)
Cell-cell signalling in bacteria	216	(1)
Quorum sensing	216	(8)
Bacterial cytokines	224	(1)
Bacterial reception of host signals	225	(3)
Concept check	228	(1)
Signalling in the paradigm organisms	229	(3)
Streptococcus pyogenes	229	(1)
Intracellular signalling	229	(1)
Intercellular signalling	229	(1)
Host-bacteria signalling	230	(1)
Escherichia coli	230	(1)
Intracellular signalling	230	(1)
Intercellular signalling	231	(1)
Host-bacteria signalling	231	(1)
What's next?	232	(1)
Questions	232	(1)
Further reading	233	(3)
Internet links	236	(2)
The mucosal surface: the front line of antibacterial defence	238	(40)
Introduction	239	(1)
An overview of antibacterial defence	239	(2)
The mucosal surface	241	(5)
Epithelial cells and epithelia	242	(4)
Mucosal antibacterial defences	246	(14)
The mucosal surface as a physical barrier to bacteria	246	(2)
Antibacterial chemicals produced by the mucosae	248	(1)
Antibacterial biomolecules produced by the mucosae	248	(1)
Mucin	249	(1)
Lysozyme	249	(2)
Lactoferrin	251	(1)
Lactoperoxidase	252	(1)
Secretory phospholipase A2	253	(1)
Secretory leukocyte protease inhibitor	253	(1)
Trefoil peptides	253	(1)
Acute phase proteins	254	(1)
Collectins	254	(1)
Secretory IgA	254	(1)
Antibacterial peptides	255	(5)
Overview of the synthesis of antibacterials by mucosal epithelial cells	260	(1)
The mucosal epithelium as a shedding surface	260	(3)
The normal microflora as an antibacterial agent	263	(3)
Other cell populations in mucosal epithelia	266	(3)
M cells	266	(2)
Paneth cells	268	(1)
Intra-epithelial lymphocytes	269	(1)
The mucosal epithelium as a watchdog	269	(2)
Concept check	271	(1)
The paradigm organisms and mucosal surfaces	272	(3)
Streptococcus pyogenes	272	(1)
Escherichia coli	273	(2)
What's next?	275	(1)
Questions	275	(1)
Further reading	275	(2)
Internet links	277	(1)
Immune defences against bacteria	278	(75)
Introduction	279	(1)
How would you design an immune system to defend yourself against bacteria?	280	(2)
The cell populations involved in immunity to bacteria	282	(12)
Monocytes, macrophages, dendritic cells	283	(2)
Granulocytes	285	(2)
Mast cells and basophils	287	(1)
Lymphocytes	288	(4)
M cells	292	(1)
Vascular endothelial cells	292	(2)
The soluble effector molecules of inflammation and immunity	294	(4)
Acute phase proteins	294	(1)
Complement system	295	(1)
Antibodies	296	(1)
Cytokines	297	(1)
Organization of the immune system	298	(5)
Innate immunity	303	(18)
How do you recognise a pathogen?	304	(1)
Pattern recognition receptors	304	(3)
Drosophila, Toll, Toll-like receptors and the Ips locus	307	(1)
Complement: a recognition and effector system of antibacterial defence	308	(6)
Phagocytes and phagocytosis of bacteria	314	(1)
Receptors involved in phagocytosis	314	(4)
Phagosomes, vesicular transport and generation of the phagolysosome	318	(1)
Bacterial killing in the phagolysosome	319	(2)
Acquired immunity	321	(23)
Generation of diversity (GOD)	323	(1)
Major histocompatibility complex proteins and antigen presentation	324	(1)
MHC proteins	324	(2)
An introduction to antigen presentation	326	(11)
Functions of effector T cell populations	337	(3)
CD4 effector mechanisms: Th1 and Th2 lymphocytes	340	(1)
The Th1/Th2 paradigm	340	(1)
Generation of Th1 and Th2 lymphocytes	341	(1)
Effector functions of Th1 lymphocytes	342	(2)
A brief overview of the immune response to bacterial infections	344	(3)
Concept check	347	(1)
Immune defences and the paradigm organisms	347	(2)
Streptococcus pyogenes	347	(1)
Escherichia coli	348	(1)
What's next?	349	(1)
Questions	349	(1)
Further reading	350	(1)
Internet links	351	(2)
Bacterial adhesion as a virulence mechanism	353	(52)
Introduction	353	(2)
To what do bacteria adhere?	355	(5)
Adhesion to external body surfaces	355	(2)
Adhesion to internal surfaces	357	(1)
Adhesion under the microscope - to what do bacteria really adhere?	358	(2)
Mechanisms involved in bacterial adhesion	360	(13)
Pre-adhesion events	360	(2)
Adhesive interactions	362	(1)
Hydrophobic interactions	362	(1)
Cation-bridging	363	(1)
Receptor-ligand binding	363	(1)
Bacterial structures involved in adhesion	364	(1)
What bacterial structures are involved in adhesion?	364	(3)
What is the nature of the adhesins on the structures involved in adhesion?	367	(3)
Host molecules functioning as receptors	370	(3)
Tissue tropism	373	(2)
Consequences of bacterial adhesion	375	(18)
Effects on the bacterium	376	(1)
Effects on the host	377	(1)
Epithelial cells	377	(12)
Fibroblasts	389	(1)
Endothelial cells	390	(2)
Phagocytic cells	392	(1)
Prevention of bacterial adhesion	393	(2)
Concept check	395	(1)
Adhesion of the paradigm organisms	395	(4)
Strcptococcus pyogenes	395	(4)
Escherichia coli	399	(1)
What's Next?	399	(1)
Questions	400	(1)
Further reading	401	(3)
Internet links	404	(1)
Bacterial invasion as a virulence mechanism	405	(61)
Introduction	405	(4)
Invasion mechanisms	409	(32)
Invasion of epithelial cells	412	(1)
Invasion involving actin rearrangements	413	(19)
Invasion involving microtubules	432	(1)
Paracytosis	433	(2)
Invasion of vascular endothelial cells	435	(1)
Neisseria meningitidis	435	(1)
Listeria monocytogenes	436	(1)
Citrobacter freundii	437	(1)
Bartonella henselae	437	(1)
β-Haemolytic streptococci	437	(1)
Streptococcus pneumoniae	437	(4)
Consequences of invasion	441	(6)
Effects on host cells	441	(1)
Cytokine release	442	(1)
Prostaglandin release	443	(1)
Effects on the expression of adhesion molecules and neutrophil adhesion	443	(1)
Cell death	444	(1)
Synthesis of tissue factor	444	(2)
Effects on bacteria	446	(1)
Bacterial survival and growth subsequent to invasion	447	(9)
Intracellular lifestyle	448	(1)
Survival within vacuoles	448	(4)
Survival in the cytoplasm of the host cell	452	(3)
Extracellular lifestyle	455	(1)
Concept check	456	(1)
Invasion of host cells by the paradigm organisms	456	(5)
Streptococcus pyogenes	456	(2)
Escherichia coli	458	(3)
What's next?	461	(1)
Questions	461	(1)
Further reading	462	(3)
Internet links	465	(1)
Bacterial exotoxins	466	(48)
Introduction	466	(1)
Classification of toxins by their activity	467	(1)
Type I (membrane-acting) toxins	468	(5)
Stable toxin (ST) family	469	(3)
Bacterial superantigens	472	(1)
Type II (membrane-damaging) toxins	473	(14)
Channel-forming toxins	473	(1)
Channel formation involving β-sheet-containing toxins	473	(4)
Channel formation involving α-helix-containing toxins	477	(1)
`Thiol-activated' cholesterol-binding cytolysins	478	(5)
RTX toxins	483	(4)
Toxins that damage membranes enzymically	487	(1)
Phospholipases	487	(1)
Proteases	487	(1)
Type III (intracellular) toxins	487	(18)
AB5 toxins	489	(1)
The cholera toxin paradigm	489	(3)
Same, organization, different function: Shiga toxins are N-glycosidases	492	(4)
ADP-ribosylation is a common toxin activity	496	(1)
Pertussis toxin, a variant AB5 design	496	(1)
ADP-ribosyltransferases of Pseudomonas aeruginosa	497	(1)
Binary ADP-ribosylating toxins	498	(1)
Other AB toxin activities	498	(1)
Glucosyltransferase	498	(1)
Deamidase	499	(1)
Protease	500	(1)
Adenylyl cyclase	501	(1)
Type III secretion and toxin 'injection'	502	(1)
Yersinia spp.	503	(1)
Pseudomonas aeruginosa	503	(1)
Type IV secretion and toxin `injection'	504	(1)
Toxins as therapeutic agents	505	(2)
Vaccines	505	(1)
Mucosal vaccines	505	(1)
Chimeric Immunotoxins	506	(1)
Muscle spasms	507	(1)
Concept check	507	(1)
Toxins produced by the paradigm organisms	507	(3)
Streptococcus pyogenes	507	(2)
Escherichia coli	509	(1)
What's next?	510	(1)
Questions	511	(1)
Further reading	511	(2)
Internet links	513	(1)
Bacterial evasion of host defence mechanisms	514	(69)
Introduction	514	(2)
Evasion of immune defences at mucosal Surfaces	516	(4)
Evasion of secretory IgA	516	(3)
Evasion of antibacterial peptides	519	(1)
Cytokines in antibacterial defence: mechanisms of microbial evasion	520	(12)
Modulins	522	(2)
Virokines and viroceptors	524	(1)
Virokines	525	(2)
Viroceptors	527	(1)
Cytokine transcription	527	(1)
Bacterial evasion of cytokines	527	(5)
Evasion of innate immune mechanisms	532	(16)
Complement evasion	532	(1)
Bacterial capsules	533	(1)
Proteases and complement evasion	533	(1)
Interference with complement regulatory proteins	534	(3)
Evasion of phagocytic killing	537	(1)
Evasion of killing by means of type III secretion systems	538	(2)
Intracellular parasitism: a novel mechanism to evade phagocytosis	540	(7)
Evasion of antigen processing	547	(1)
Evasion of acquired immunity	548	(10)
Evasion of antibodies	550	(1)
Bacterial immunoglobulin-binding proteins	550	(1)
Antigenic variation	551	(3)
Superantigens and evasion of T lymphocyte responses	554	(4)
Bacterial control of the cell cycle and apoptosis as evasion mechanisms	558	(17)
Bacterial inhibition of cell cycle progression	558	(1)
The eukaryotic cell cycle	558	(1)
Bacterial proteins with the ability to control cell cycle progression	559	(4)
Bacterial control of apoptosis	563	(1)
The mechanism of apoptosis	564	(5)
Bacterial control of the apoptotic process	569	(6)
Concept check	575	(1)
Evasion of host defences by the paradigm organisms	575	(3)
Streptococcus pyogenes	575	(1)
Escherichia coli	576	(2)
What's next?	578	(1)
Questions	578	(1)
Further reading	578	(4)
Internet links	582	(1)
Bacteria in human health and disease: the future?	583	(32)
Introduction	583	(2)
Identification of bacterial virulence genes and virulence mechanisms in vivo	585	(4)
Caenorhabditis elegans and bacterial virulence	586	(1)
Study of bacterial pathogenic mechanisms in humans	587	(2)
Development of new antibacterials	589	(5)
Inhibition of bacterial adhesion	590	(2)
Antibacterial peptides	592	(1)
Antisense	592	(1)
Other approaches	592	(1)
New targets from genomics	593	(1)
Using genomics to identify vaccine candidates	594	(1)
Genomics to identify the basics of life	594	(1)
Bacteria and idiopathic diseases	595	(9)
Helicobacter pylori, ulcers and cancer	597	(1)
Bacteria and heart disease	598	(4)
Other diseases possibly caused by bacteria	602	(1)
Psoriasis	602	(1)
Kidney stones	602	(1)
Asthma and the hygiene hypothesis	603	(1)
Conversations with the normal microflora	604	(7)
Vibrio fischeri and the bobtail squid	604	(3)
The mammalian intestine: another host-microbe interface	607	(1)
Alterations in intestinal anatomy/renewal in gnotobiotic mice	607	(2)
Alterations in the GALT of gnotobiotic mice	609	(1)
Alteration in epithelial cell differentiation in gnotobiotic mice	609	(2)
Wolbachia pipientis and insect reproduction	611	(1)
Summary	611	(1)
Further reading	612	(2)
Internet links	614	(1)
Appendix A. Glossary of terms used	615	(18)
Appendix B. Brief descriptions of bacteria frequently mentioned	633	(6)
Index	639