Microbial Pathogenesis: Evasion, Invasion & Damage

• The chapter discusses the mechanisms of host evasion, invasion, and damage

Microbial Pathogenesis Overview

• Most pathogens target a specific host receptor for entry and adherence
• Portals of entry include mucous membranes (respiratory, gastrointestinal, genitourinary tracts), conjunctiva, skin, and parenteral routes

Entry Point

• Mucous membranes, skin, and the parenteral route are general portals of exit, mirroring entry points
• Pathogens can cause multiple diseases if they have multiple entry portals

Host Defense

• Pathogens penetrate or evade host defenses using capsules, cell wall components, enzymes, antigenic variation, invasins, and intracellular growth
• Siderophores, direct damage, toxins (exotoxins, endotoxins), lysogenic conversion, and cytopathic effects contribute to host cell damage

Host Cell Damage

• It occurs through siderophores, direct damage, toxins like exotoxins and endotoxins, lysogenic conversion, and cytopathic effects
• Damage can involve the host cell wall or membrane, or an attempt to hide or mimic host structures

Evasion of Host Defenses - Bacteria

• Bacteria evade host defenses through various mechanisms
• They avoid detection by hiding out, forming biofilms, or using capsules
• Bacteria use antigenic variation to change their surface structure and block phagocytosis via capsules and cell wall components

Evasion of Host Defenses - Viruses

• Viruses evade the host defenses via antigenic variation

Antigenic Variation

• It involves changes to surface proteins that make pathogens unrecognizable to existing antibodies

Mechanisms to Penetrate and Invade Host Tissues

• Some mechanisms that penetrate and invade host tissues also allow the pathogen to evade host defenses

Bacterial Exoenzymes

• Bacteria exit the microorganism and use specific substrates at an increased rate to speed up a response
• They are extracellular enzymes produced by bacteria to target specific host components

Purpose and Results

• Invade host tissues by immune evasion and access to nutrients
• Coagulases: Hides in blood clots and contains nutrients. Induces blood clot formation and utilizes nutrients, but runs out
• Kinases: Digests fibrin, which breaks down the blood clot and produces streptokinase
• Hyaluronidase: Digests hyaluronic acid, which holds the epithelial cells together with Clostridium perfringens
• Collagenase: Breaks down the collagen, which holds the cells together with Clostridium species
• IgA Proteases: Destroys IgA antibodies found in secreted fluids of Neisseria meningitidis and Neisseria gonorrhoeae

Invasins

• Invasins are surface proteins that rearrange actin filaments in the host cell cytoskeleton.
• Entering the host cells requires moving between cells

Examples

• Salmonella Typhurium, membrane ruffling
• Listeria Monocytogenes, Actin tails

Host Cells Damage

• Four basic ways pathogens damage host cells: using host nutrients, causing direct damage, producing toxins, and inducing hypersensitivity (allergic) reactions
• Virulence factors mediate all four for invading host cells and disease

Bacterial Damage to Host Cells

• Siderophores are iron-binding proteins secreted by bacteria that take magnets from the host
• They bring back pathogens to bacterium, nutrients used during infection to prevent bacteria

Direct Damage

• Direct damage overlaps with an invasion of host tissue
• Exoenzymes access nutrients, and are an immune evasion
• Invasins rearrange surface proteins with actin filaments on the cytoskeleton host
• Cell lysis leads to rapture to host cell and is mediated via toxins

Bacterial Toxin Production

• Toxins are poisonous substances produced by certain microorganisms
• It is a fever in the cardiovascular system, can cause disturbances, diarrhea, and shocks when one inhibits protein syntheses
• Toxemia is the presence of toxins in blood
• 2 types, exotoxins and endotoxins

Toxin Effects

• Effects caused by presence of a toxin, not microbial growth; food infection versus food intoxication
• Intoxications happen within seconds

Exotoxins

• Are released outside the bacterial cell

Food Intoxication vs Food Infection

• Food infection versus food intoxication depending on if there is an infection taking place
• Symptoms of food infection take hours, while food intoxication takes days

Exotoxins Characteristics

• Produced inside bacteria and secreted into the environment as gram positive bacteria, rapidly transported
• Exotoxins act on a specific host target and produce characteristic symptoms
• Antitoxins are used in vaccines with inactivated toxins

Exotoxins and Disease

• Affect specific cells and cause disease and are toxic substances released outside the cell

Three Major Groups of Exotoxins

• They are divided based on structure and function

Types of Exotoxins

• A-B toxins
• Membrane-disrupting toxins
• Superantigens

A-B Toxins

• They consist of two proteins, A an active protein and B to bind the protein

A-B Toxin Method

• The B protein gets the material into the host cell, and then the A protein causes the damage

A-B Toxin Examples

• Botulinum toxin
• Tetanus toxin
• Cholera toxin
• Diphtheria toxin
• Anthrax toxin
• Shiga toxin
• VacA
• Genotoxins
• Tetanus Toxin*
• Prevents the release of glycine and GABA, which prevent muscle relaxation
• Glycine allows nerves to stop releasing acetycholine, which contracts muscles
• Botulinum*
• Blocks the release of acetycholine, which stops muscle contraction