Bacterial Stress Response ppt

Bacterial Stress Response Mechanisms

  • Key mechanisms encoded in core and accessory genomes.

Learning Outcomes

  • Understand key bacterial stress response mechanisms.
  • Define diversity and mechanisms of toxin-antitoxin systems.

Bacterial Resilience

  • Resistance: Ability to withstand challenges (Darby et al., 2022)
    • Types:
    • Genetically Encoded Resistance Systems: Based on genetic factors.
    • Metabolically Inactive State: Temporary dormancy.
    • Aggregates & Biofilms: Structures providing protection.
  • Tolerance: Capability to survive stressful conditions over time.
  • Persistence: Long-lasting presence in adverse conditions.

Gene Regulation in Bacteria

  • Transcriptional Regulation:
    • Involves activators and repressors.
    • Utilizes transcription factors.
  • Post-Transcriptional (Translational) Regulation:
    • Mechanisms include mRNA cleavage, action of sRNA and RNA-binding proteins.
    • Affects:
    • mRNA Stability: Maintains mRNA integrity.
    • Protein Activity: Modifications influencing functionality.
  • Post-Translational Regulation:
    • Involves protein-protein interactions and modifications (e.g. phosphorylation).
    • Impacts protein localization, stability, and activity.

Sigma Factors

  • Essential proteins found in bacterial core genomes.
  • Critical for initiation of transcription:
    • Sab Factors in Escherichia coli:
    • 70 (RpoD): Housekeeping sigma factor for normal growth.
    • 54 (RpoN): Nitrogen assimilation.
    • 38 (RpoS): Regulation during stationary phase and stress response.
    • 32 (RpoH): Heat shock response.
    • 28 (FliA): Genes related to flagella.
    • 24 (RpoE): Response to misfolded proteins.
    • 19 (Fecl): Iron transport.

General Stress Response

  • RpoS Regulation:
    • Regulates over 400 genes across various levels:
    • Gene transcription, mRNA translation, protein stability, and activity.

Stringent Response

  • Involves signaling nucleotides:
    • Guanosine Tetraphosphate (ppGpp): Alarmone involved in stress response.
    • DksA: Transcription factor that works with ppGpp.
    • RelA: GTP pyrophosphokinase critical in this pathway.

Accessory Genome & Toxin-Antitoxin Systems

  • Accessory Genes:
    • Located on plasmids, transposons, genomic islands, and prophages.
    • Include antibiotic resistance and virulence factors, metabolic adaptations, stress mechanisms, and CRISPR-Cas systems.
  • Roles of Toxin-Antitoxin Systems:
    • Induce dormancy or lysis, provide antiphage defense, facilitate stress tolerance, and support the survival of persister cells.

Classification of Toxin-Antitoxin Systems

  • Bipartite Systems: Eight types based on antitoxin mode of action.
  • Tripartite Systems: Such as retron toxin-antitoxin systems.

Toxin Families and Their Functions**

  • Type II Toxin-Antitoxin Systems:
    • CcdB, ParE: Act on the DNA-gyrase complex, inhibit replication.
    • MazF, HicA: Ribosome-independent mRNA interferases, inhibit translation.
    • RelE, HigB: Ribosome-dependent mRNA interferases, target translation.
  • Additional families affect peptidoglycan synthesis and ribosome binding.

Complex Network of Toxin-Antitoxin Systems

  • Exhibit cross-talk and regulate stress response gene expression.

Summary of Learning Outcomes

  • Describe key bacterial stress response mechanisms.
  • Understand general stress response, stringent response, sigma factors, and toxin-antitoxin systems.