Human pathogens

Mortality in men (WHO –2002) 32% due to infectious and parasitic disease –HIV 15% –Diarrhoea 10% –TB 9% –DTP Polio Measles 6% 2% in European region –HIV18% –Diarrhoea8% –TB35% –DTP Polio Measles3%

meet the pathogens...

Yersinia pestis peculiarly virulent -host death promotes flea dispersal has caused 200 million human deaths blocks flea midgut inhibits inflammatory response in mice Yersinia pseudotuberculosis "enteric lifestyle" wide host range but narrow tissue range survives in environment causes gastroenteritis in humans

Mycobacterium tuberculosis

Helicobacter pylori

Capetown A Capetown B Maori European

Trypanosoma brucei gambiense

Some miscelleneous thoughts about pathogens...

they can be quite ingenious in their transmission mechanisms

Dicrocoelium dendriticum

They can evolve rapidly (and generally to intermediate virulence)..

Neisseria meningitis Others cause symptoms that are paradoxical

Summary about myself MEng in Electronic and Information Engineering, University of Cambridge Life Sciences Interface, Doctoral Training Centre, University of Oxford

Samples We do not have a sequenced ST-213 reference genome 8 pools sequenced simultaneously –42 Oxford carriage strains divided into 4 pools(pools 1&2 1998/99; pools 3&4 2000/01) –67 Great Britain disease strains divided into 4 pools (pools 5&6 1998/99; pools 7&8 2000/01) –A serogroup C vaccine was introduced between these dates Strains unlabelled within pools

Solexa sequencing DNA sequencing with Solexa technology –1 billion bases of DNA per run –Typical read lengths 30-50bp –~2.5million reads per pool (30× coverage) –Quality score –Differential amplification? Example reads from pool 1: Solexa quality score

The body has an elaborate set of mechanisms that allow it to control infections caused by most organisms found in the environment

Pathogens often evolve in response to herd immunity

Plasmodium vivax Schistosoma mansoni Eukaryotic pathogens typically have multiple hosts in their lifecycle

Virulent host specific lineages often arise multiple times from the a single cosmopolitan species

Virulent lineages are often recent in origin and show substantial genome rearrangement and degradation

"So, Nat'ralist observe, a Flea Hath smaller Fleas that on him prey, And these have smaller Fleas to bite 'em, And so proceed ad infinitum." Pathogens have their own pathogens T4 bacteriophage

Lytic phage

Lysogenenic phage

A little bit about pathogen dynamics