Pathogenesis

Pathogenesis

• Refers to the development and progression of diseases caused by pathogens.

• Invade host → survive and multiply → find a new host

  • Tools used for these tasks are virulence factors

Pathogens

• Definition: Microorganisms including bacteria, viruses, fungi, or protozoa that cause diseases.

• Not all pathogens are bacteria; many are viral or fungal.

• Most bacteria are harmless, and only a small minority are pathogenic.

Structure and Function of Viruses

• Viruses consist of DNA or RNA as their genetic material.

• They can mutate, leading to different variants (strain variations).

• Laboratory techniques for detecting viruses include PCR (Polymerase Chain Reaction) and antigen testing.

• Example: Early research and genome sequencing began in 2020 for Covid 19

Major Groups of Microorganisms (Phyla)

• Includes diverse species like:

• Bacteria: Includes pathogens like Staphylococcus aureus, Escherichia coli, and Vibrio cholerae.

• Fungi: Generally non-pathogenic but some are opportunistic.

• Protozoa: Can cause diseases like malaria.

Virulence Factors

• Attributes of pathogens that enable them to cause disease

• Categories of virulence factors:

  • Adhesins: Allow attachment to host cells (pili or fimbriae).

    • Ex: Type I and Type IV pili of E.coli : type 1 attach to host cells; type 4 twitching, extension and contraction

    • Pili/fimbriae contribute to biofilm formation

    • Biofil poses serious problems for chronic infections and are hard to cure

  • Toxins: Exotoxins are secreted protein toxins that disrupt host function, classified into five main types:

    • Cell membrane disrupters (e.g., hemolysins)

      • Hemolysin is produced by Staphylococcus aureus (infects and inflames one or more hair follicles; boil)

      • Forms a transmembrane pore in target membranes

    • Protein synthesis disrupters (e.g., Shiga toxin)

      • Shiga toxin responsible for gastrointestinal illnesses; produced by certain strands of E.coli

        • Ex. E. coli O157:H7 (Chipotle)

      • AB Toxins

        • A subunit: has toxic activity

        • B subunit: B binds specifically to host cells and delivers A subunit to cytoplasm; B subunits oftern form a pore for A to enter the cell

      • Cholera

        • Outbreak in Hait in 2010

        • Vibrio cholerae (rod shaped)

      • Anthrax

        • USA attack, 2001

        • Bacillus anthracis

        • 2 active toxins:

          • Edema factor raises cAMP levels and causes fluid secretion, tissue swelling

          • Lethal factor cleaves protein kinases and blocks immune system from attack

      • Tetanus and botulism

        • Affect our neurons

        • Botulism: muscle always relaxed

          • Clostridium botulinum (food-borne)

        • Tetanus: muscle continually contracts

          • Clostridium tetani (rusty nail)

        • Gram positive, spore forming anaerobes

        • Have similar sequences and structures

        • Act by blocking the release of neurotransmitters

    • Second messenger pathway disrupters

    • Superantigens

    • Proteases

  • Secretion systems

    • Gram-negative bacteria need to export proteins through the outmembrane

    • Secretion systems I-VI

      • Type I Secretion: Direct from cytoplasm to environment.

      • Type II Secretion: Resembles type IV pili (can extand/retract); proteins travel to the periplasm before secretion

        • Ex. Cholera toxin

      • Type III Secretion: Injects proteins directly into host cells, resembling a syringe; homologous to flagellum

      • Type IV Secretion: Can secrete proteins or DNA from cytoplasm or periplasm, involved in horizontal gene transfer.

        • Agrobacterium tumefaciens

        • Bordetella pertussis

Pathogenicity Islands

• Virulence factors are often encoded on pathogenicity island

  • DNA looks different and oftenhas indications of lateral gene transfer

    • Signature GC%

    • Flanked by tRNA and repetitive DNA

    • phage and plasmid genes

    • toxin genes

• Example:

  • Locus of enterocyte attachment (LEE) codes for proteins necessary for colonization and disease development and uses type 3 secretion system

  • O157 plasmid encodes multiple genes, some related to adherence and acidic resistance

  • STX associated bacteriophages codes for verotoxin type 1 and or 2

Gene regulation

• two-component signal transduction

  • detect mg, sugar, pH, etc

• Quorum sensning

  • delays toxin synthesis until many bacteria are present