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Regulation of Virulence Genes

Regulation of Virulence Genes

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Regulation of Virulence Genes

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  1. Regulation of Virulence Genes Salyers & Whitt: Bacterial Pathogenesis: A Molecular Approach ASM Press, 1994 Dorman, C.J: Genetics of Bacterial Virulence. Blackwell Scientific Publications, 1994

  2. Virulence Factors • Invasion • Penetration • Protection • Nutrition • Dissemination

  3. Overview • Gene Regulation • Genetic Organization • In Vitro Methods for Studying Virulence Factors • Protein Secretion

  4. Environmental Pressures Influencing Virulence Factor Production • Osmolarity • O2 Concentration • CO2 Concentration • pH • O2 and N intermediates • Lack of nutrients • Inorganic ion concentrations

  5. Environmental Modulation vs Phase Variation Antigenic Variation

  6. Genetic Variation in Pathogenic Bacteria • Homologous Recombination • Slip Strand Mispairing • Opa – N. gonorrhoeae – CTCTT • LPS – H. influenzae – CAAT • Pilin – H. Influenzae – TA • Site-specific Recombination • Gene Inversion • Flagellin - S. typhimurium

  7. Phase Variation I: Gene Inversion

  8. Stages in interaction of N.gonorrhoeae with cultured mammalian cells

  9. pilE Antigenic Variation

  10. Phase Variation II: Slipped Strand Mispairing

  11. Transcriptional Regulation • Fur repressor (ferric uptake repression) • AraC transcriptional activator family • LysR transcriptional activator family • Two-Component Regulatory Systems

  12. Ara C Family

  13. LysR Transcriptional Activator Family

  14. Membrane Signal Transduction

  15. Genetic Organization of Virulence Factors: Sources • Plasmid transformation(horizontal gene transfer) e.g Shigella flexneri, Salmonella spp, Yersinia spp, Clostridium tetani. • Phage lysogeny e.g C. botulinus toxins,S. pyogenes, C. diphtheria toxin, Cholera toxin • Pathogenicity Islands • Transposons • Integrons

  16. Pathogenicity Islands • Carriage of many virulence genes • Association with pathogenic species • Different GC content compared to rest of host genome • Association with tRNA genes and/or insertion sequence elements, suggesting phage origin. • Presence of transposable elements • Instability