Microbial Pathogenicity: Invasiveness & Toxigenesis

Microbial Pathogenicity

• Refers to the ability of microbes to cause disease
• Pathogenic microbes cause disease through invasiveness and toxigenesis

Invasiveness

• The ability to invade tissues
• Colonization is essential for pathogens to establish within a host, involving adherence to tissues, multiplication, and evasion of immune responses for further growth and invasion.
• Involves production of extracellular substances to facilitate invasion
• Allows microbes to bypass or overcome host defense mechanisms

Toxigenesis

• The ability to produce toxins
• Bacteria produce two primary types of toxins: exotoxins, which are secreted into the environment, and endotoxins, which are components of the bacterial cell wall that are released upon cell lysis.

Exotoxins

• Released from bacterial cells
• Can act at tissue sites remote from bacterial growth

Endotoxins

• Cell-associated substances
• Bacterial toxins, categorized as either soluble or cell-associated substances, possess the ability to circulate through the host's bloodstream and lymphatic system. This transportation mechanism enables them to exert cytotoxic effects on various tissues that are distant from the site of initial microbial invasion. As a result, even remote tissues can experience significant damage, contributing to the overall pathology of the infection.

Colonization Factors

• Specific recognition of receptor sites on target cells enhances pathogenic advantage
• Capsules serve as protective layers that not only enhance adherence to host tissues but also play a crucial role in helping pathogens evade detection and neutralization by the host's immune system, thereby facilitating sustained colonization and infection.
• Surface receptors/target sites exist both on bacteria (adhesins) and the host (target)
• Examples include fimbriae of Enterobacteriaceae, Chlamydia binding to host N-acetyl-D-glucosamine (a cell surface lectin), and protein adhesin of Mycoplasma

Invasive Factors

• Enable pathogenic microorganisms to enter and spread throughout the host tissues

Degradative Enzymes

• Proteins that catalyze reactions
• Bacterial and host enzymes both play roles in the disease process

Toxigenicity

• Microorganisms ability to cause disease as determined by the toxin it produces
• The type and potency of the toxin produced significantly influence the overall virulence of the microorganism.

Endotoxin

• Endotoxin is an integral component of the outer membrane of Gram-negative bacteria, composed mainly of lipopolysaccharides. This structural feature not only functions as a barrier that protects the bacterial cell from environmental stresses but also plays a critical role in triggering immune responses within the host organism upon release. When bacteria undergo cell lysis, endotoxins are released into the host's circulation, leading to the activation of the immune system, which can result in inflammation and other systemic effects. The presence of these molecules in the bloodstream can consequently lead to symptoms ranging from fever to septic shock, highlighting their significance in pathogenesis.
• Released only upon lysis of the cell which means the cell degrades

Exotoxins

• These are a potent toxic substance formed and secreted by certain bacteria

Adherence Factors

• Pathogenic bacteria colonize mucosal sites using pili (fimbriae) to adhere to cells

Invasion Factors

• Surface components that allow bacteria to invade host cells
• These genetic elements can be located either on plasmids, which are mobile DNA fragments, or integrated into the bacterial chromosome, allowing for diverse inheritance patterns.

Capsules

• Bacteria are surrounded by capsules
• Capsules provide a physical barrier that hinders the immune system's ability to mark bacteria for destruction and limits their engulfment by immune cells.

Endotoxins

• Lipopolysaccharide endotoxins on Gram-negative bacteria cause fever, changes in blood pressure, inflammation, lethal shock, and other toxic events

Exotoxins

• Protein toxins and enzymes from pathogenic bacteria
• Include cytotoxins, neurotoxins, and enterotoxins

Siderophores

• Iron-binding factors that can compete with the host for iron
• Iron is bound to hemoglobin, transferrin, and lactoferrin

Non-Specific Resistance

• Lysozyme
• Mucous
• Skin
• Respiratory tract
• Gastrointestinal tract
• Urogenital tract
• Conjunctiva
• Commensals of the natural flora
• Phagocytosis
• Inflammatory response
• Fever
• Biochemical and tissue constituents

Antibodies

• Neutralization
• Complement recruitment
• Opsonization

Inflammatory Process - Congestion Phase

• Capillaries become engorged and dilated with blood
• Increases capillary permeability due to the reaction of endothelial cells
• This increased blood causes heat and redness

Inflammatory Process - Leakage

• Leukocytes migrate out of the capillaries into surrounding tissues
• Neutrophils are prominent early on, while monocytes and lymphocytes migrate later
• Monocytes clear debris

Inflammatory Process - Phagocytosis

• Specialized cells defend the body, engulfing invading microorganisms and cell debris to speed healing

Serous Fluids - Transudates

• Fluid is pushed through the capillary as a result of high hydrostatic pressure generated by the blood, facilitating nutrient and gas exchange in tissues.

Serous Fluids - Exudates

• Fluid that leaks around the cells of the capillaries, caused by inflammation