Evolution of enteric pathogens

1
Evolution of enteric pathogens
2
family Enterobacteriacea

• Genera
• Human, animal pathogens
• Salmonella, Yersinia, Aeromonas, E.coli/Shigella
• Commensals/symbionts of animals
• E.coli, Citrobacter
• Plant pathogens
• Erwinia
• Environmental bacteria
• Aeromonas, Klebsiella
• Why so different?
• Links to plant-related past?
• Most grow on plant-derived sugars
• Salmonella, E.coli cannot break down pectin.
  Yersinia, Klebsiella can

3
Evolution of Salmonella

• Serovars are differentiated based on antigens
• O polysaccharide antigen
• H1, H2 flagella
• 2,501 serovars are recognized
• Some (sv Typhimurium, Newport) have a broad host
  range
• Gallinarum and Pullorum --gt chickens (fowl
  typhoid)
• Typhi, Parathyphi --gt primates (typhoid fever)
• Cholerasuis --gt pigs (pig paratyphoid)
• Dublin --gt cattle (bacteremia)
• Other svs are host-adapted
• Not all serovars are virulent
• Sv Bongori
• Sv Sophia
• Common in chickens in Australia, not known to
  have caused disease in humans
• All Salmonella have pathogenicity islands (SPIs)

4
SPIs

• SPIs Salmonella pathogenicity islands. Absent
  in E.coli
• SPI-1 carries genes involved in epithelial cell
  invasion. 40-kb, chromosomal
• mutants are virulent only if delivered by direct
  injection
• SPI-2 required for intracellular survival during
  infection
• even when injected, mutants are not fully
  virulent
• SPI-3 consists of 10 genes required for Mg2
  acquisition and growth in macrophages.
• Present in some serovars, lost from others
• SPI-4 carries 18 genes involved in survival
  within macrophages
• SPI-5 contains 6 genes, 4 of which are required
  for enteritis in a calf model

5
Evolution of Salmonella relatedness of subspecies
Relatedness tree is based on the relatedness of
DNA sequences of multiple genes (loci)
I
major pathogens
enterocolitis, enteric fever
VI
II
IIIb
SPI-2
Gain of SPI-1
IV
VII
IIIa
S. bongori
V
Typically non-pathogenic
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Evolution of Salmonella relatedness of subspecies
I differs from V by 8, E.coli from S. enterica
by 15 I and V diverged 65-75 mln yrs
ago Salmonella and E.coli diverged 120 mln yrs ago
I
major pathogens
enterocolitis, enteric fever
VI
II
IIIb
SPI-2
Gain of SPI-1
IV
VII
IIIa
S. bongori
V
Typically non-pathogenic
7
Evolution of virulence in E.coli

• Normally a commensal in human gut
• occupies large intestine and lower small
  intestine
• the only gut inhabitant using oxygen and thus
  maintains anaerobiosis
• virulent and commensal strains do not cluster
  separately (i.e. many commensal strains have
  closely related pathogens)
• some E.coli sv are closely related to different
  Shigella sp

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Virulent E.coli strains

• Enterotoxigenic
• plasmid-borne genes for enterotoxins
• adhesin pili
• a non-invasive pathogenic E.coli
• Enteropathogenic.
• carry LEE island encoding proteins involved in
  attachment, a protein injection system (Type 3)
• EAF plasmid with genes for adherence
• Enterohemorrhagic
• LEE island carries a phage-encoded Shiga toxin
• virulence EHEC plasmid
• Enteroaggregative
• Enteroinvasive (include Shigella)
• carry pINV
• Unlike typical E.coli, Shigella cant utilize
  lactose, mannitol are non-motile.
• Most enteroinvasive E.coli have the same
  deficiencies
• Uropathogenic

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EHEC O157H7

• Discovered in the 1980s
• Common in cattle.
• commensal in cattle
• pathogen in humans
• Virulence factors
• LEE
• stx (Shiga toxin) and EHEC plasmid are possibly
  recent acquisitions
• Evolution
• gained O157 by recombination,
• then split into two lineages sorbital-negative
  and b-glucuronidase negative
• both major lineages carry phage-encoded stx genes

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How related are E. coli?
UPEC
Commensal
3
21
7.6
includes 247 islands gt1kB
39
3
7
17
includes 108 islands gt1kB
EHEC
Loosely based on Lan and Reeves, 2006
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Evolution of Yersinia

• 11 species, only 3 are significant pathogens
• Y. pseudotuberculosis, Y. enterocolitica
• food-, waterborne pathogens that cause
  gastroenterocolitis
• share virulence factors not found in
  non-pathogenic isolates
• escape human immune system thanks to an outer
  membrane protein encoded by a 70-kB virulence
  plasmid
• carry virulence determinants (production of
  siderophore) on a High Pathogenicity Island (HPI)
• HPI is highly mobile and was found in other
  enterics
• chromosomally encoded virulence factors also
  present

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Evolution of Yersinia

• Y. pestis
• causes plague
• transmitted by fleas
• a clone of Y. pseudotuberculosis.
  Indistinguishable by common methods
• distinct from Y. pseudotuberculosis in its
  virulence strategy
• colonizes flea gut.
• genes on pFra plasmid are involved
• is transmitted to a host through a bite
• reverse blood flow during biting due to partial
  blockage of the fleas proventriculus. Blood
  meal is regurgitated. hemin storage genes are
  found in both Y. pestis and Y.
  pseudotuberculosis
• disseminates in blood from the infection site

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Population genetics of enterics

• All bacterial populations are clonal to some
  extent
• Recombination
• important source of variation
• for enterics, recombination appears more
  important then mutation
• frequency differs for different species
• Neisseria -- frequent, Salmonella -- rare
• Through recombination clones adapt to specific
  niches

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Conclusions

• Many virulence determinants are carried on mobile
  genetic elements
• Pathogenicity islands, virulence plasmids are
  shared between clones and species
• Surface antigen polymorphism
• O antigen is the main target for immune system
  and phages (high selective pressure)
• Gene decay
• Genes mutate, and loss of function is OK
• e.g. Shigella is non-motile, cant utilize
  lactose or decarboxylate lysine.
• Occupies a different niche (inside a eukaryotic
  cell) than commensal E.coli (in the gut of
  mammals where lactose is found). Making flagella
  is expensive, flagella is also an antigen