Microbial Mechanisms of Pathogenicity: How Microorganisms Cause Disease

Microbial Mechanisms of Pathogenicity

Introduction

This chapter explores the strategies and mechanisms by which microorganisms cause disease in their hosts. Understanding these mechanisms is essential for the study of infectious diseases, epidemiology, and the development of therapeutic interventions.

Pathogenicity and Virulence

Definitions

• Pathogenicity: The ability of a microorganism to cause disease in a host.

• Virulence: The degree or extent of pathogenicity, often measured by the severity of disease produced.

Portals of Entry

How Microorganisms Enter a Host

• Mucous membranes: Entry through the respiratory, gastrointestinal, and genitourinary tracts.

• Skin: Usually impenetrable, but some microbes can enter through hair follicles or sweat ducts.

• Parenteral route: Microbes are deposited directly into tissues when barriers are penetrated (e.g., cuts, bites, injections).

• Most pathogens have a preferred portal of entry that is critical for their ability to cause disease.

Numbers of Invading Microbes

Measuring Infectivity and Lethality

• ID50: Infectious dose for 50% of a sample population; measures the virulence of a microbe.

• LD50: Lethal dose for 50% of a sample population; measures the potency of a toxin.

Adherence to Host Tissues

Mechanisms of Adherence

Almost all pathogens must attach to host tissues to establish infection, a process called adherence (or adhesion).

• Adhesins (ligands) on the pathogen bind to specific receptors on host cells.

• Structures involved include the glycocalyx and fimbriae.

• Microbes may form biofilms, which are communities that share nutrients and provide protection from host defenses.

Penetration of Host Defenses

Capsules and Cell Wall Components

• Capsules: Glycocalyx layers around the cell wall that impair phagocytosis (e.g., Streptococcus pneumoniae, Bacillus anthracis).

• M protein: Resists phagocytosis (Streptococcus pyogenes).

• Opa protein: Allows attachment to host cells (Neisseria gonorrhoeae).

• Waxy lipid (mycolic acid): Resists digestion (Mycobacterium tuberculosis).

Enzymes Produced by Pathogens

• Coagulases: Coagulate fibrinogen to protect bacteria from phagocytosis.

• Kinases: Digest fibrin clots to facilitate spread.

• Hyaluronidase: Digests polysaccharides that hold cells together.

• Collagenase: Breaks down collagen in connective tissue.

• IgA proteases: Destroy IgA antibodies.

Antigenic Variation

• Pathogens alter their surface antigens, rendering host antibodies ineffective.

Penetration into the Host Cell

• Invasins: Surface proteins that rearrange actin filaments, causing membrane ruffling and facilitating entry (e.g., Shigella, Listeria).

• Some bacteria use actin to move from one cell to another.

• Survival inside phagocytes involves escaping from the phagosome, preventing lysosomal fusion, or surviving in low pH environments.

Biofilms

• Biofilms help bacteria evade phagocytes and increase resistance to immune responses due to the extracellular polymeric substance (EPS) matrix.

Using the Host’s Nutrients

Siderophores

• Iron is essential for bacterial growth; host iron is tightly bound to proteins.

• Siderophores are proteins secreted by pathogens that bind iron more tightly than host proteins, allowing bacteria to acquire iron.

Direct Damage to Host Cells

Mechanisms

• Disruption of host cell function.

• Utilization of host cell nutrients.

• Production of waste products.

• Multiplication within host cells, causing cell rupture.

Production of Toxins

Types and Effects

• Toxins: Poisonous substances produced by microorganisms that can cause fever, cardiovascular problems, diarrhea, and shock.

• Toxigenicity: Ability to produce toxins.

• Toxemia: Presence of toxins in the blood.

• Intoxications: Disease caused by toxins without microbial growth.

Exotoxins

• Proteins produced and secreted by bacteria, usually gram-positive.

• Soluble in body fluids; destroy host cells and inhibit metabolic functions.

• Antitoxins: Antibodies against exotoxins.

• Toxoids: Inactivated exotoxins used in vaccines.

A-B Toxins

• Consist of an enzyme (A part) and a binding component (B part).

• Example: Diphtheria toxin.

• Genotoxins damage DNA, causing mutations and potentially cancer.

Membrane-Disrupting Toxins

• Lyse host cells by disrupting plasma membranes.

• Leukocidins: Kill phagocytic leukocytes.

• Hemolysins: Kill erythrocytes by forming protein channels.

• Streptolysins: Hemolysins produced by streptococci.

Superantigens

• Cause intense immune responses by stimulating T cells to release cytokines.

• Symptoms include fever, nausea, vomiting, diarrhea, shock, and death.

Diseases Caused by Exotoxins

Disease	Bacterium	Type of Exotoxin	Mechanism
Botulism	Clostridium botulinum	A-B	Neurotoxin prevents transmission of nerve impulses; flaccid paralysis results.
Tetanus	Clostridium tetani	A-B	Neurotoxin blocks nerve impulses to muscle relaxation; results in muscle spasms.
Diphtheria	Corynebacterium diphtheriae	A-B	Cytotoxin inhibits protein synthesis, especially in heart, nerve, and kidney cells.
Cholera	Vibrio cholerae	A-B	Enterotoxin causes secretion of large amounts of fluids and electrolytes, leading to diarrhea.
Anthrax	Bacillus anthracis	A-B	Two A components enter the cell via the same B. The A components cause shock and reduce immune response.
Traveler's diarrhea	Escherichia coli	A-B	Enterotoxin causes secretion of fluids and electrolytes from intestinal cells.
Gas gangrene and food poisoning	Clostridium perfringens	Membrane-disrupting	One toxin causes massive red blood cell destruction; another is related to food poisoning.
Staphylococcal food poisoning	Staphylococcus aureus	Superantigen	Toxin causes secretion of fluids and electrolytes from intestines, leading to diarrhea.

Endotoxins

• Lipid A portion of lipopolysaccharides (LPS) in the outer membrane of gram-negative bacteria.

• Released during bacterial multiplication and when bacteria die.

• Stimulate macrophages to release cytokines, which can cause fever, shock, and disseminated intravascular coagulation.

Pyrogenic Response

• Endotoxins induce macrophages to release cytokines, which act on the hypothalamus to produce prostaglandins, resulting in fever.

Detection of Endotoxins

• Limulus amebocyte lysate (LAL) assay: Uses horseshoe crab blood cells that clot in the presence of endotoxin.

Comparison of Exotoxins and Endotoxins

Property	Exotoxins	Endotoxins
Bacterial Source	Gram-positive and gram-negative bacteria	Gram-negative bacteria
Relation to Microorganism	Metabolic product of growing cell	Present in LPS of outer membrane; released on cell death
Chemistry	Proteins, usually with two parts (A-B)	Lipid portion (lipid A) of LPS
Fever?	No	Yes
Neutralized by Antitoxin?	Yes	No
LD50	Small	Relatively large

Genetic Elements and Pathogenicity

Plasmids and Lysogeny

• Plasmids may carry genes for toxins, antibiotic resistance, and enzymes.

• Lysogenic conversion occurs when a bacteriophage integrates into the host genome, altering microbial characteristics.

Pathogenic Properties of Viruses

Cytopathic Effects (CPE)

• Visible effects of viral infection on host cells.

• Include stopping cell synthesis, lysosomal enzyme release, formation of inclusion bodies, syncytium formation, chromosomal changes, and loss of contact inhibition (may lead to cancer).

Interferons

• Alpha and beta interferons are produced by virally-infected cells.

• They protect neighboring cells by inhibiting viral protein synthesis and inducing apoptosis in infected cells.

Pathogenic Properties of Fungi, Protozoa, Helminths, and Algae

Fungi

• Produce toxic metabolic products and provoke allergic responses.

• Trichothecene toxins inhibit protein synthesis.

• Proteases modify host cell membranes; capsules prevent phagocytosis.

• Some produce ergot (hallucinogenic alkaloids), aflatoxin (carcinogenic), and mycotoxins (neurotoxic).

Protozoa

• Cause symptoms by their presence and waste products.

• Avoid host defenses by digesting cells, growing in phagocytes, and antigenic variation.

Helminths

• Use host tissue for growth, produce large masses, and cause cellular damage.

• Release waste products that cause symptoms.

Algae

• Some produce neurotoxins, such as saxitoxin, leading to paralytic shellfish poisoning.

Portals of Exit

How Microorganisms Leave the Host

• Respiratory tract: Coughing and sneezing.

• Gastrointestinal tract: Feces and saliva.

• Genitourinary tract: Urine and secretions.

• Skin and blood: Via arthropod bites, needles, or syringes.

Additional info: This summary integrates and expands upon the provided lecture slides and textbook images, ensuring a comprehensive overview of microbial pathogenicity mechanisms for microbiology students.