Microbial Mechanisms of Pathogenicity

Introduction

This chapter explores how microorganisms cause disease, focusing on the mechanisms by which pathogens invade hosts, evade defenses, and inflict damage. Understanding these processes is essential for microbiology students to grasp the basis of infectious diseases and host-pathogen interactions.

Pathogenicity and Virulence

Definitions

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

• Virulence: The degree or extent of pathogenicity; a measure of the severity of disease caused by a microbe.

How Microorganisms Enter a Host

Portals of Entry

Pathogens must enter the host through specific portals to initiate infection. Most pathogens have a preferred portal of entry, which influences their ability to cause disease.

• Mucous membranes: Includes the respiratory tract (most common), digestive canal, genitourinary system, and conjunctiva.

• Skin: Generally impenetrable unless compromised; entry possible via hair follicles or sweat gland ducts.

• Parenteral route: Direct deposition into tissues beneath the skin or mucous membranes (e.g., injections, bites, wounds, surgery).

Example: Respiratory tract infections (e.g., influenza) are acquired by inhalation of airborne pathogens.

Numbers of Invading Microbes

Infectious and Lethal Doses

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

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

Adherence to Host Tissues

Mechanisms of Adherence

Pathogens must attach to host tissues to establish infection. This process is mediated by adhesins (ligands) on the pathogen that bind to specific receptors on host cells.

• Glycocalyx: Example—Streptococcus mutans uses a dextran-based glycocalyx to adhere to teeth.

• Fimbriae: Example—Actinomyces fimbriae adhere to the glycocalyx of S. mutans.

• Viral spikes: Example—SARS-CoV-2 spikes bind to ACE2 receptors on host cells.

Penetration or Evasion of Host Defenses

Capsules

• Composed of glycocalyx; protect bacteria from phagocytosis.

• Examples: Streptococcus pneumoniae (pneumonia), Haemophilus influenzae (pneumonia, meningitis), Bacillus anthracis (anthrax), Yersinia pestis (plague).

Cell Wall Components

• M protein: Resists phagocytosis (Streptococcus pyogenes).

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

• Mycolic acid: Waxy lipid resists digestion by phagocytes (Mycobacterium tuberculosis).

Enzymes

• Coagulases: Coagulate fibrinogen to form clots.

• Kinases: Digest fibrin clots.

• Hyaluronidase: Digests hyaluronic acid, aiding tissue penetration.

• Collagenase: Breaks down collagen.

• IgA proteases: Destroy IgA antibodies.

Antigenic Variation

• Pathogens alter their surface antigens to evade host immune responses.

• Examples: Influenza virus, Neisseria gonorrhoeae, Trypanosoma brucei gambiense.

Penetration into the Host Cell

• Invasins: Surface proteins that rearrange host cell actin, causing membrane ruffling and bacterial engulfment (e.g., Shigella, Listeria).

• Some bacteria survive inside phagocytes by escaping the phagosome, preventing lysosomal fusion, or requiring low pH for survival.

Biofilms

• Communities of microorganisms encased in a protective matrix (EPS).

• Resist antibiotics, disinfectants, and phagocytosis; involved in 65% of all infections.

Using the Host’s Nutrients

Siderophores

• Proteins secreted by pathogens to bind iron more tightly than host iron-binding proteins.

• Iron is essential for bacterial growth and pathogenicity.

Direct Damage to Host Cells

• Disruption of host cell function.

• Consumption of host nutrients.

• Production of waste products.

• Cell rupture due to microbial multiplication.

Production of Toxins

General Concepts

• Toxins: Poisonous substances produced by microorganisms.

• Toxigenicity: Ability to produce toxins.

• Toxemia: Presence of toxins in the blood.

• Intoxications: Disease caused by toxins without microbial growth.

Exotoxins

Exotoxins are proteins secreted by bacteria, usually gram-positive, that are highly specific and potent. They can be neutralized by antitoxins and inactivated for use in vaccines (toxoids).

• A-B toxins: Consist of an active (A) and binding (B) component (e.g., diphtheria toxin).

• Genotoxins: Damage DNA, potentially leading to mutations and cancer.

• Membrane-disrupting toxins: Lyse host cells by disrupting plasma membranes (e.g., leukocidins, hemolysins, streptolysins).

• Superantigens: Trigger excessive immune responses, causing fever, shock, and death.

Endotoxins

Endotoxins are lipid A components of lipopolysaccharides (LPS) in the outer membrane of gram-negative bacteria. They are released upon bacterial death and can cause fever, shock, and disseminated intravascular coagulation.

• Stimulate macrophages to release cytokines, leading to fever and inflammation.

• May weaken the blood-brain barrier and cause endotoxic shock.

Table: Comparison of Exotoxins and Endotoxins

Pathogenic Properties of Viruses

Mechanisms for Evading Host Defenses

• Intracellular location shields viruses from immune detection.

• Attachment to host cell surface molecules facilitates entry.

• Some viruses attack immune system components or mimic host molecules (e.g., methylation of viral RNA).

• Antigenic variation allows evasion of immune responses.

Cytopathic Effects (CPE)

• Visible effects of viral infection on host cells.

• Cytocidal effects: Kill host cells.

• Noncytocidal effects: Cause cell damage without death.

• Examples: Disruption of cell junctions, cytokine storms, inclusion bodies (e.g., Negri bodies in rabies), syncytium formation.

Interferons

• Alpha and beta interferons are produced by virally infected cells to protect neighboring cells.

• They inhibit viral protein synthesis and induce apoptosis in infected cells.

• Some viruses can evade interferon responses.

Pathogenic Properties of Fungi

• Produce toxic metabolic products and provoke allergic responses.

• Proteases modify host cell membranes (e.g., Candida albicans).

• Capsules prevent phagocytosis (e.g., Cryptococcus neoformans).

• Aflatoxin (by Aspergillus) is carcinogenic; mycotoxins from mushrooms are neurotoxic.

Pathogenic Properties of Algae

• Some produce saxitoxin, a neurotoxin causing paralytic shellfish poisoning.

• Associated with red tides (blooms of Alexandrium).

• Toxin accumulates in mollusks, which can poison humans upon consumption.

Portals of Exit

Pathogens exit the host via specific routes, often the same as their portals of entry.

• Respiratory tract: Coughing, sneezing

• Gastrointestinal tract: Feces, saliva

• Genitourinary tract: Urine, genital secretions

• Skin

• Blood: Via arthropod bites, needles, or syringes

Summary Diagram: Microbial Mechanisms of Pathogenicity