Med mic Ex 3

Study Guide - Smart Notes

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Bacterial Pathogenesis and Virulence Factors

Adhesion and Fimbriae

Bacterial adhesion to host tissues is a critical first step in pathogenesis. Many bacteria use specialized surface structures, such as fimbriae (pili), to attach to host cells and initiate infection.

Fimbriae: Hair-like appendages on the bacterial surface that mediate attachment to host cells. The term 'mannose sensitive fimbriae' refers to fimbriae that bind to mannose residues on host cell surfaces and can be inhibited by free mannose.
Non-fimbrial adhesins: Surface proteins or structures other than fimbriae that facilitate bacterial attachment. Their localization and structure can differ between Gram-positive and Gram-negative bacteria.
Example: Streptococcus pneumoniae uses surface proteins to adhere to lung epithelium, which can be investigated by gene knockout and adhesion assays.

Type III Secretion System (T3SS)

The Type III secretion system is a needle-like protein apparatus used by many Gram-negative bacteria to inject effector proteins directly into host cells, manipulating host cell functions to the pathogen's advantage.

Function: Delivers virulence factors into host cells, subverting immune responses and promoting infection.
Tissues: Commonly found in pathogens infecting intestinal, respiratory, and urogenital tracts.
Example: Enteropathogenic Escherichia coli (EPEC) uses T3SS to disrupt host cell cytoskeleton and signaling.

Invasion and Pathogenicity

Invasion refers to the ability of pathogens to enter, survive, and multiply within host tissues. Not all pathogens are invasive; some remain extracellular.

Invasive Pathogens: Enter host cells or tissues (e.g., Salmonella spp.).
Non-invasive Pathogens: Remain on epithelial surfaces (e.g., Vibrio cholerae).
Tissue Tropism: The preference of a pathogen for specific tissues, determined by host cell receptors and pathogen adhesins.

Actin Polymerization and Cell-to-Cell Spread

Certain bacteria, such as Listeria monocytogenes, use actin polymerization to move within and between host cells, facilitating cell-to-cell spread without exposure to the extracellular environment.

Mechanism: Bacterial surface proteins (e.g., ActA) recruit host actin, forming comet tails that propel bacteria.
Flagella: Not required for intracellular movement in Listeria.
Advantage: Avoids immune detection by minimizing extracellular exposure.

Bacterial Capsules and Immune Evasion

Bacterial capsules are polysaccharide layers that surround some bacteria, protecting them from host immune responses.

Composition: Can be made of hyaluronic acid (e.g., Streptococcus pyogenes), sialic acid, or other polysaccharides.
Function: Inhibits phagocytosis and complement activation.
Example: Neisseria meningitidis capsule contains sialic acid, mimicking host molecules.

M-Protein and Other Surface Proteins

M-protein is a major virulence factor of Streptococcus pyogenes, located on the bacterial surface.

Function: Inhibits opsonization and phagocytosis by binding host factors.
Location: Anchored in the cell wall of S. pyogenes.

Capsule Synthesis and Targeting

Some bacteria produce capsular polysaccharides (CPS) that are important for virulence and immune evasion.

Genes: CPS synthesis is encoded by specific gene clusters.
Targeting: Bacterial toxins and effectors may have specific mechanisms to reach their host targets, such as receptor-mediated entry.

Streptococcus Dysgalactiae and Protein G

Streptococcus dysgalactiae produces protein G, a surface protein that binds immunoglobulins.

Function: Binds the Fc region of IgG, interfering with opsonization and immune clearance.

Antibody Isolation and Protein A

Protein A from Staphylococcus aureus is used in laboratory settings to purify antibodies from complex mixtures.

Mechanism: Binds the Fc region of IgG, allowing for affinity purification.
Application: Used in immunoprecipitation and antibody purification protocols.

Homologous Recombination

Homologous recombination is a genetic process where similar or identical DNA sequences exchange genetic information.

Orientation: Can occur between direct repeats (same orientation) or inverted repeats (opposite orientation).
Importance: Facilitates DNA repair, genetic diversity, and horizontal gene transfer.

Antibiotic Resistance and Diphtheria Toxin

Bacteria can develop resistance to antibiotics through various mechanisms, including target modification, efflux pumps, and enzymatic degradation.

Diphtheria Toxin: A single subunit A of diphtheria toxin can inactivate multiple elongation factors in a eukaryotic cell, halting protein synthesis.

Summary Table: Bacterial Virulence Factors

Virulence Factor	Function	Example Organism
Fimbriae	Adhesion to host cells	Escherichia coli
Type III Secretion System	Injection of effectors into host	Salmonella enterica
Capsule	Immune evasion	Streptococcus pneumoniae
M-protein	Prevents phagocytosis	Streptococcus pyogenes
Protein A	Binds IgG Fc region	Staphylococcus aureus

Key Equations and Concepts

Homologous Recombination:

Capsule Synthesis: Encoded by cps gene clusters in many bacteria.

Additional info: Some explanations and examples have been expanded for academic completeness and clarity.