Dissecting virulence of E. coli O157: H7 using genome alignments Escherichia coli is a normal resident of the mammalian gut

Dissecting virulence of E. coli O157:H7 using genome alignments

Escherichia coli is a normal resident of the mammalian gut

• Escherichia coli is a normal resident of the mammalian gut

• Most strains are non-pathogenic
• E. coli K12 – lab strain
• Some strains are pathogenic to human: E. coli O157:H7
• Cause diarrhea, cramps
• The most virulent strains of O157:H7 can result in death

• Disease symptoms caused in part by the bacterial production of Shiga toxin

• Shiga toxins act to inhibit protein synthesis in the host
• Cytotoxic

• Pathogenic strains transmitted through consumption of contaminated foods, (undercooked ground meat products/vegetables watered with contaminated water)

Microbes living in or on a host AND

• Microbes living in or on a host AND

• Producing negative consequences to host

• Killing host cells
• Inducing an immune response in host (toxic shock)
• Reducing the “fitness” of the host

• Virulence factors are proteins that facilitate the microbes ability to exploit the host

Virulence = severity of damage to the host

• Virulence = severity of damage to the host

• Things produced by the bacterial that make the host sicker
• Example: Shiga toxin in enterohemorraghic E. coli

• Why would a pathogen “want” to harm the host?

• Virulence is sometime a byproduct of the bacterial efforts to live and propagate in a host
• Proteins that adhere to host cells
• Proteins injected into the host to manipulate the host cell
• Stx encodes a protein that facilitates attachment to the host mucosa, but it also inhibits protein synthesis in the host cell

Pathogenic bacteria and virulence factors

14 categories of virulence factors for E. coli O157:H7

Differ in degree of virulence

• Differ in degree of virulence

• Most virulence factors are not yet known

• How can we begin to make hypotheses about which genes play roles in the virulence of different strains?

Comparison of the genome structire of pathogenic vs. non-pathogenic strains indicate that pathogenesis is associated with multi-gene “islands”

• Comparison of the genome structire of pathogenic vs. non-pathogenic strains indicate that pathogenesis is associated with multi-gene “islands”

• The functions of some of the genes could be inferred using BLAST

• genes encoding type III secretion system, adhesins, and phage- and plasmid-encoded genes

Background information regarding epidemiology of E. coli O157:H7 outbreaks

As of 2010, there are 15 E. coli O157:H7 genomes sequenced. We will have you focus on three that are all in the ASAP database (http://asap.ahabs.wisc.edu/asap/home.php)

Comparative genomics using the tool Mauve: Multiple Genome Aligner

Student individual projects

Here is a list of a few virulence factors