Steps in Bacterial Pathogenesis

Overview of Pathogenesis

Bacterial pathogenesis refers to the process by which bacteria cause disease in a host organism. This involves a series of coordinated steps that enable bacteria to colonize, invade, and damage host tissues while evading immune defenses.

• Reservoirs: Natural habitats where bacteria reside before infecting a host.

• Transmission: Movement of bacteria from the reservoir to the host.

• Entry to the host's body: Bacteria gain access through portals such as mucous membranes, skin, or wounds.

• Adhesion to the host's tissue: Bacteria attach to host cells using adhesins or other surface molecules.

• Invasion: Colonization and growth within the host's tissue: Bacteria penetrate and multiply within host tissues.

• Production of toxins: Bacteria secrete substances that damage host cells and tissues.

Tissue damage and disease result from the combined effects of bacterial growth, invasion, and toxin production.

Invasion Mechanisms and Strategies

Internalization into Non-Phagocytic Host Cells

Bacteria employ various strategies to invade host cells that do not normally engulf particles (non-phagocytic cells). These mechanisms allow bacteria to penetrate cellular barriers and evade immune responses.

• Penetration of cellular barriers: Bacteria cross epithelial or endothelial layers to access deeper tissues.

• Protection from the immune system: Internalization shields bacteria from immune detection and attack.

Production of Spreading Factors

Spreading factors are enzymes produced by bacteria to facilitate invasion into deeper tissues and promote dissemination within the host.

• Invasion into deeper tissues: Enzymes degrade extracellular matrix components, allowing bacteria to spread.

• Killing of host cells: Some factors directly damage host cells, aiding bacterial survival and spread.

Evasion from the Immune System

Bacteria have evolved mechanisms to avoid detection and destruction by the host immune system, ensuring their survival and persistence.

• Capsule formation: Capsules prevent phagocytosis and antibody recognition.

• Mimicry of host molecules: Bacteria may express surface molecules similar to host components to avoid immune detection.

Internalization Strategies

Binding and Focussing of Host Membrane Proteins

Bacteria such as Yersinia use surface proteins (e.g., invasin) to bind host cell integrins, triggering actin polymerization and subsequent phagocytosis.

• Actin-polymerization: Rearrangement of the host cytoskeleton facilitates bacterial uptake.

• Example: Yersinia invasin binds to α1β1-integrins on epithelial cells, leading to internalization.

Injection of Enzymes into Host Cell

Bacteria such as Salmonella inject effector proteins into host cells via specialized secretion systems, manipulating host cell processes to promote invasion.

• Type III Secretion System: Delivers virulence factors (e.g., SopE, SptP) directly into host cells.

• Actin-polymerization: Induced by bacterial effectors, resulting in membrane ruffling and bacterial uptake.

• Example: Salmonella typhimurium and S. typhi infect intestinal mucosa and cause diarrhea or typhoid fever.

Key Enzymes and Their Actions

• SopE: Activates small GTP-binding protein CDC42, promoting actin rearrangement.

• SptP: Dephosphorylates phosphotyrosine in proteins, aiding cytoskeletal rearrangement.

Intracellular Motility and Spread

Some bacteria, such as Listeria monocytogenes, move within and between host cells by hijacking the host's actin cytoskeleton.

• Actin-polymerization: Bacteria induce actin assembly at one pole, propelling themselves through the cytoplasm.

• Spread to adjacent cells: Enables dissemination without exposure to extracellular immune defenses.

• Example: Listeria monocytogenes binds to E-cadherin, is internalized, escapes the phagosome via listeriolysin O, and spreads by actin-based motility.

Production of Spreading Factors

Enzymatic Factors Facilitating Invasion

Bacteria secrete enzymes that degrade host tissues, facilitating deeper invasion and dissemination.

Evading the Immune System

Capsule-Mediated Evasion

Bacterial capsules are polysaccharide layers that protect against phagocytosis and antibody recognition.

• Prevention of phagocytosis: Capsules physically block immune cell access.

• Molecular mimicry: Capsules containing sialic acid and hyaluronic acid resemble host molecules, preventing antibody formation.

Protein-Mediated Evasion

Bacteria express surface proteins that bind host proteins, masking themselves from immune detection.

• M-Protein: Streptococcus pyogenes binds fibrinogen, protecting against antibody binding.

• Cna-Protein: Staphylococcus aureus binds collagen, aiding immune evasion.

Summary Table: Immune Evasion Mechanisms

Key Terms and Concepts

• Actin-polymerization: The assembly of actin filaments, used by bacteria to move within host cells.

• Phagocytosis: The process by which cells engulf particles; bacteria may induce or evade this process.

• Type III Secretion System: A needle-like structure used by Gram-negative bacteria to inject effector proteins into host cells.

• Virulence factors: Molecules produced by pathogens that contribute to the pathogenicity and facilitate invasion, immune evasion, or tissue damage.

Relevant Equations and Molecular Structures

• Actin Polymerization:

• GTPase Activation (CDC42):

• Depolymerization of Hyaluronic Acid:

Examples and Applications

• Yersinia: Utilizes invasin to bind integrins and induce uptake by epithelial cells.

• Salmonella: Injects SopE and SptP to manipulate host cytoskeleton and promote internalization.

• Listeria monocytogenes: Moves within and between cells using actin-based motility, evading extracellular immune defenses.

Additional info: Academic context and definitions have been expanded for clarity and completeness. Tables have been reconstructed and summarized for study purposes.