Pathogenic Escherichia coli

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Pathogenic Escherichia coli
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Escherichia coli Characteristics

• Discovered in 19th century by Bavarian
  pediatrician Theodor Escherich
• Gram negative eubacteria
• Facultative anaerobe
• Usually motile
• Universal inhabitant of human (mammalian) colon

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E. coli Lives in Colon of Healthy People (member
of commensal flora)
Includes E. coli
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E. coli
Enteroinvasive E. coli

• agent of bacillary dysentery

• member normal gut flora

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Dysenteric Colon
Normal Colon

• diseased GI tract
• Fever
• Severe abdominal pain
• Bloody discharge with mucous

• healthy GI tract

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Bacterial pathogens express traits not present in
non-pathogenic ancestors

• Commensal bacteria cannot invade or survive in
  new host niches
• new selective pressures such as nutrient
  deprivation, immune molecules, and cells unique
  to hostile host environments
• Pathogens express new biochemical pathways and
  whole systems of novel traits that enable access
  to and survival in these unique environments
• Enteroinvasive E. coli penetrate intestinal
  epithelial cells and spread to adjacent cells
• complex traits likely encoded by multiple genes

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Expected E. coli non-pathogen to pathogen
relationship
E .coli
Pathogenic E .coli
Time
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Invasive E. coli evolved from distinct ancestors
Enteroinvasive E .coli lineages
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• Complex new multi-subunit trait essential for
  invasive pathogenic E. coli virulence
• Virulence traits that damage the host often
  encoded by multiple genes in pathogenicity
  islands

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Pathogen evolution incompatible with classical
evolution models

• Classical evolution model new traits evolve
  through modifications to established genes
• Slow process of individual base changes in
  ancestral genes
• Pathogens close relationship with commensal
  bacteria suggests virulence traits evolve rapidly
• How do bacterial pathogens rapidly evolve from
  non-pathogenic organisms?

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How Can E. coli be both a Commensal and a
Pathogen?
Genome sequences revolutionizing understanding of
bacterial evolution
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How Can E. coli be both a Commensal and a
Pathogen?
DIFT colored dashes in MG1655 represent genes not
present other E. coli
WHITE dashes represent genes not present in MG1655
E. coli isolates (strains) have different genome
compositions
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Mechanisms of Horizontal Gene Transfer (HT)
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• Bacterial genomes are mosaics of old and new
  genes
• New genes identified by unique sequence
  characteristics
• New genes often associated with mobile genetic
  elements

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• New genes rarely confir a selective advantage
• Survival of HT loci in host genome dependent on
  the ability to confer a beneficial trait to the
  host
• i.e. a gain-of-function mutation (rare)
• Gain-of-function mutations usually requires
  multiple genes encoding whole systems
• HT loci comprising operons have best chance for
  success
• Gain-of-function mutations may permit occupation
  of a new niche
• HT loci contribute to speciation

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Pathogenic E. coli evolved from distinct ancestors
Enteropathogenic E .coli
Enteroinvasive E .coli
Enterotoxigenic E .coli
Enterohaemorrhagic E .coli
Uropathogenic E .coli
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Pathogenic E. coli Diseases - Generalities

• Associated with three clinical syndromes
• diarrhoeal disease
• urinary tract infections
• sepsis/meningitis
• Pathogenic E. coli diseases usually result from
  ingestion of virulent organisms in contaminated
  food and water
• Signs and symptoms most often include those
  associated with intestinal infections
• diarrhea
• abdominal discomfort
• fever
• additional complications possible

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Pathogenic E. coli Virulence Mechanisms
Generalities

• Virulence systems frequently encoded on mobile
  genetic elements
• successful combinations reflected in pathotypes
• Like other mucosal pathogens, pathogenic E. coli
  use multi-step strategy to infect host
• attachment
• evasion of host defenses
• multiplication
• damage host
• Pathogenic E. coli often colonize host niches
  not normally inhabited by E. coli

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Enteropathogenic E. coli (EPEC)

• First E. coli pathotype described
• UK pediatrician John Bray, 1945
• Causes potentially fatal infant diarrhea in
  developing areas
• Contract organism by ingestion of contaminated
  water, food or fomites

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EPEC Colonization and Lesion Development

• patchy colonization of the small intestine
• Generates unique histopathology termed
  attaching and effacing lesion
• destroys microvilli
• Expresses numerous toxins/effectors that
  manipulate host cell systems to serve the
  pathogen
• EPEC, like other pathogenic E. coli strains, is
  a master cell biologist

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EPEC A/E Lesion and Pedestal Formation
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Type III Secretion Systems Inject Toxins into
Host Cells
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EPEC LEE Pathogenicity Island

• encodes EPEC Type III secretion system and
  toxins/effectors
• toxins/effectors essential for EPEC attachment
  and pedestal formation

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EPEC is a Master Cell Biologist

• Toxins/effectors activities
• promote EPEC adherence
• disrupt host cytoskeleton
• disrupt cytokinesis
• promote cell death (apoptosis)
• disrupt tight junctions

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Consequences of EPEC Toxin/effector Actions

• Diarrhea may result from combination of ion
  imbalance, malabsorption and/or inflammation
• To date, no diarrheal toxin known identified

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Enterohaemorrhagic E. coli (EHEC)

• First described in 1982
• Causes bloody diarrhea (haemorrhagic colitis),
  non-bloody diarrhea and haemolytic uremic
  syndrome (HUS)
• 5 of EHEC infections result in HUS
  predominantly in children lt5 years old and
  elderly
• 5 of HUS cases are fatal
• Contract organism by ingesting contaminated food
• common inhabitant of bovine gut
• low infectious dose for humans (lt100 organisms)
• organism may be resistant to stomach acid

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EHEC Ecology and Transmission
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EHEC Virulence Factors

• O157H7 serotype dominant in North America, UK,
  Japan
• O26 and O111 serogroups more prominent in other
  countries
• Evolved from LEE containing EPEC serogroup O55
• Like EPEC, generates A/E lesion
• Colonizes the large intestine
• Expanded repertoire of adhesion factors
• Encodes toxins/effectors in EPEC LEE
• Additional virulence factors (plasmid and
  chromosomal)
• RTX toxin similar to haemolysin
• StcE activates host Complement cascade
• Stx (Shiga) toxin

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Stx (Shiga) Toxin

• Toxin encoded on bacteriophage
• gt200 E. coli serotypes encode Stx
• Shiga toxin E. coli (STEC)
• most do not encode LEE (not virulent)
• A/B toxin
• pentameric B subunits bind holotoxin to host
  cell surface
• A subunit cleaves host ribosomal RNA arresting
  protein synthesis and cell death (apoptosis)
• Stx produced in colon travels through
  bloodstream to kidney
• Damages renal endothelium and induces
  inflammation that may lead to acute renal failure
  and death

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HUS Stx (Shiga) Toxin Activity
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Review

• E. coli samples new genes from the environment
  only those that encode a selective advantage are
  maintained
• Pathogenic E. coli evolved from non-pathogenic
  commensal strains
• Virulence is multifactorial
• Pathogenic E. coli are master cell biologists