Genetics of Pathogens Life styles of pathogen

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Genetics of Pathogens

  • Life styles of pathogen

  • Methods to identify genes needed for virulence

  • Environmental signals for virulence gene regulation

  • Specific Examples

The Main Points of Pathogenesis

  • The pathogens are usually one step ahead

  • The host is one step behind

  • Why are we not all dead?

  • We are not all dead nor are all pathogens eliminated?

  • Bacteria do not have brains and they do not seek you out.

  • The purpose of a bacterium is to make bacteria.

  • Life does not exist in pure culture.

  • Life does not exist in logarithmic growth-stationary phase

  • and hungry is the usual state

  • Sometimes, the bacteria/virus makes mistakes-too virulent. Influence pandemic-HIV?

  • Sometimes, the bacteria/virus is not virulent enough.

Robert Koch (1876)

  • Koch's postulates

    • find microorganism in all cases of the disease, that are absent in healthy animals
    • isolate the microorganism from diseased host in pure culture
    • infect a healthy animal with the microorganism and get the same disease
    • Isolate the same microorganism in pure culture from the infected host

Molecular Koch’s Postulates.

  • The phenotype or property under investigation should be associated with pathogenic members of a genus or pathogenic species.

  • Specific inactivation of the gene(s) associated with the suspected virulence trait should lead to a measurable loss in pathogenicity or virulence.

  • Reversion of the mutated gene should lead to restoration of pathogenicity: complementation.

  • Current molecular pathogenesis research is held to this standard. It is not always possible to satisfy the third rule for technical or physiological reasons.

Results of a lot of mutant hunts

  • Pathogens contain genes not found in their closely related counter parts

  • Genes specific to the pathogens are organized into islands, islet, atolls. That is, specific regions that are unique to the pathogens.

  • Pathogenicity islands encode those functions needed for the pathogen to causes a successful infection. It still needs the rest of the chromosome!

  • Pathogenicity islands have different G+C content than the backbone chromosome. Islands tend to be A+T rich, especially in Salmonella and E.coli.

  • PA’s can encode a specialized secretion apparatus designed to transfer effector proteins into the host. The proteins are specifically designed to alter host cell function. The proteins usually interact with a specific host protein or class of proteins.

  • Some but not all PA’s have inserted in a rare tRNA seltRNA. This insertion event does not interrupt the tRNA, but provides a powerful selection for the PA’s presence.

Salmonella Pathogenesis - INTRODUCTION

  • Salmonella is an enteric pathogen capable of infecting a wide variety of vertebrate hosts

  • Not all infected hosts exhibit clinical symptoms of Salmonella infection

  • Non-typhoidal Salmonella serotypes cause enteritis and occasional systemic infection

  • Certain Salmonella serovars exhibit host adaptation but the mechanisms are poorly understood

  • Salmonella is a facultative intracellular pathogen adapted to survival in host mononuclear phagocytes

  • Genetic tools are available to dissect virtually every aspect of the Salmonella-host interaction

Great Moments in Salmonella History

  • First isolated by Theobald Smith. S. Choleraesuis from porcine intestine around 1885. He worked for Daniel Salmon, who had nothing to do with the work.

  • 1829- P.Ch.A. Louis in Paris separated typhoid from other fevers.

  • 1884-Gaffkey Germany isolated Salmonella Typhi from spleens of infected patients

  • 1896- first heat killed vaccine by Pfeiffer and Kalle.

  • 1920 to 1940-Kaufman and White developed the serotype classification of Salmonella

  • 1952-Zinder and Lederberg-discovered genetic transduction using phage P22

  • 1973-Bruce Ames developed the “Ames Test” to determine mutagenic activity of chemicals

  • September 1984-Salmonella Typhimurium used to restaurants in the The Dalles, OR.

“Typhoid Mary” was Mary Mallon

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