Evolution of enteric pathogens

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					Evolution of enteric pathogens

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

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 --> chickens (fowl typhoid) Typhi, Parathyphi --> primates (typhoid fever) Cholerasuis --> pigs (pig paratyphoid) Dublin --> 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)

• SPI’s = 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

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


SPI-2 Gain of SPI-1 IV

IIIa V S. bongori
Typically non-pathogenic

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


SPI-2 Gain of SPI-1 IV

IIIa V S. bongori
Typically non-pathogenic

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

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 can’t utilize lactose, mannitol are non-motile. – Most enteroinvasive E.coli have the same deficiencies

• Uropathogenic

EHEC O157:H7
• 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

How related are E. coli?
UPEC Commensal 7.6% 39% 3% 7% 3% 21%
includes 247 islands >1kB

includes 108 islands >1kB

Loosely based on Lan and Reeves, 2006

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 nonpathogenic 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

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 flea’s proventriculus. Blood meal is regurgitated. hemin storage genes are found in both Y. pestis and Y. pseudotuberculosis

• disseminates in blood from the infection site

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

• 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, can’t 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

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