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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. Virulence Factors. Invasion Penetration Protection Nutrition Dissemination. Overview.
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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
Virulence Factors • Invasion • Penetration • Protection • Nutrition • Dissemination
Overview • Gene Regulation • Genetic Organization • In Vitro Methods for Studying Virulence Factors • Protein Secretion
Environmental Pressures Influencing Virulence Factor Production • Osmolarity • O2 Concentration • CO2 Concentration • pH • O2 and N intermediates • Lack of nutrients • Inorganic ion concentrations
Environmental Modulation vs Phase Variation Antigenic Variation
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
Stages in interaction of N.gonorrhoeae with cultured mammalian cells
Transcriptional Regulation • Fur repressor (ferric uptake repression) • AraC transcriptional activator family • LysR transcriptional activator family • Two-Component Regulatory Systems
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
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