Regulation of Virulence Genes

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

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Environmental Modulation vs Phase
Variation Antigenic Variation
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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

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Phase Variation I Gene Inversion
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Stages in interaction of N. gonorrhoeae with
cultured mammalian cells
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pilE Antigenic Variation
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Phase Variation II Slipped Strand Mispairing
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Transcriptional Regulation

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

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Ara C Family
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LysR Transcriptional Activator Family
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Membrane Signal Transduction
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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

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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