Microbial Mechanisms of Pathogenicity PDF

CHAPTER 6: MICROBIAL MECHANISMS OF PATHOGENICITY   Pathogenicity: Ability of a microorganism to cause disease HOW A by overcoming host defenses. MICROORGANISM  Virulence: Degree of ENTERS A HOST pathogenicity, indicating...

CHAPTER 6: MICROBIAL MECHANISMS OF PATHOGENICITY   Pathogenicity: Ability of a microorganism to cause disease HOW A by overcoming host defenses. MICROORGANISM  Virulence: Degree of ENTERS A HOST pathogenicity, indicating how severe the disease can be.  Mechanisms of Disease Pathogens typically must: HOW A ▪ Gain access to the host. MICROORGANISM ▪ Adhere to host tissues. ENTERS A HOST ▪ Penetrate or evade host defenses. ▪ Damage host tissues (some cause disease through waste products instead).  Portals of Entry Mucous Membranes HOW A  Common entry points for MICROORGANISM bacteria and viruses: ENTERS A HOST  Respiratory tract: Most frequent portal; diseases include common cold, pneumonia, tuberculosis, influenza, and measles.  Portals of Entry Mucous Membranes HOW A  Common entry points for bacteria and viruses: MICROORGANISM  Gastrointestinal tract: Pathogens ENTERS A HOST enter via food, water, or contaminated fingers; diseases include poliomyelitis, hepatitis A, typhoid fever, and cholera.  Portals of Entry Mucous Membranes HOW A  Common entry points for bacteria and viruses: MICROORGANISM  Genitourinary tract: Entry ENTERS A HOST through sexual contact; STIs include HIV, genital warts, chlamydia, syphilis, and gonorrhea.  Portals of Entry Skin HOW A  Largest organ and primary defense MICROORGANISM against pathogens: ENTERS A HOST ▪ Unbroken skin is generally impenetrable. ▪ Microbes can enter through hair follicles, sweat glands, or breaks in the skin (e.g., cuts or abrasions). ▪ Some pathogens can penetrate intact skin (e.g., hookworm larvae).  Portals of Entry HOW A Conjunctiva MICROORGANISM ENTERS A HOST  Mucous membrane covering the eyes ▪ Can be a portal for infections like conjunctivitis and trachoma.  Portals of Entry Parenteral Route HOW A Entry through direct tissue MICROORGANISM deposition: Occurs via punctures, ENTERS A HOST injections, bites, cuts, wounds, or surgical procedures. Pathogens transmitted this way include HIV and hepatitis viruses.  Preferred Portal of Entry Many pathogens have a specific portal of entry essential for causing disease. HOW A Examples: MICROORGANISM ▪ Salmonella typhi: Causes typhoid fever when ingested; minimal reaction occurs ENTERS A HOST if applied to skin. ▪ Streptococcus pneumoniae: Causes pneumonia when inhaled; does not typically cause symptoms if swallowed. ▪ Yersinia pestis & Bacillus anthracis: Can cause disease through multiple portals of entry.  Preferred Portal of HOW A Entry MICROORGANISM ENTERS A HOST  Infection Threshold: A few microbes may be neutralized by host defenses, but large numbers increase the likelihood of disease.  Preferred Portal of Entry  ID50 (Infectious Dose): Indicates the number of pathogens needed to infect HOW A 50% of a population; varies by pathogen and portal: MICROORGANISM ▪ Bacillus anthracis: ENTERS A HOST ▪ Cutaneous: 10-50 endospores ▪ Inhalation: 10,000-20,000 endospores ▪ Gastrointestinal: 250,000-1,000,000 endospores ▪ Vibrio cholerae: ID50 is 108 cells; neutralizing stomach acid reduces required dose.  Preferred Portal of Entry Toxin Potency HOW A  LD50 (Lethal Dose): Indicates the dose needed to kill 50% of a MICROORGANISM population; varies significantly ENTERS A HOST among toxins: ▪ Botulinum toxin: 0.03 ng/kg (highly potent) ▪ Shiga toxin: 250 ng/kg ▪ Staphylococcal enterotoxin: 1350 ng/kg  Adherence  Almost all pathogens require adherence to host tissues for HOW A pathogenicity. MICROORGANISM  Adhesins: Surface molecules on ENTERS A HOST pathogens that bind to specific receptors on host cells; often glycoproteins or lipoproteins.  Examples of Adhesion Structures: ▪ Glycocalyx ▪ Pili, fimbriae, and flagella  Biofilms  Communities of microorganisms that adhere to surfaces and share HOW A nutrients. MICROORGANISM  Formation: ENTERS A HOST ▪ Initial attachment by bacteria leads to multiplication and secretion of glycocalyx. ▪ Biofilms can be multi-layered and consist of various microbial species.  Biofilms HOW A MICROORGANISM  Significance: Biofilms resist disinfectants and antibiotics, ENTERS A HOST complicating treatment in infections involving medical devices or dental plaque.  Adherence Pathogen Examples HOW A  Streptococcus mutans: Attaches to MICROORGANISM teeth using glycocalyx; contributes ENTERS A HOST to dental plaque and caries.  Enteropathogenic E. coli: Uses fimbriae adhesins to attach to specific intestinal cells.  Treponema pallidum (syphilis): Uses a tapered end for attachment.  Adherence HOW A Pathogen Examples MICROORGANISM  Listeria monocytogenes: Produces ENTERS A HOST adhesins for specific host cell receptors.  Neisseria gonorrhoeae: Utilizes fimbriae for attachment in genitourinary tract and other areas. HOW BACTERIAL PATHOGENS Most pathogens must penetrate host PENETRATE HOST tissues to cause disease, although DEFENSES some can damage surface tissues.  Capsules HOW BACTERIAL  Glycocalyx material forming a protective capsule around bacterial PATHOGENS cell walls. PENETRATE HOST  Function: DEFENSES ▪ Increases virulence by resisting phagocytosis. ▪ Prevents phagocytic cells from adhering to the bacteria.  Capsules HOW BACTERIAL  Examples: PATHOGENS ▪ Streptococcus pneumoniae: Virulent PENETRATE HOST strains have capsules; avirulent DEFENSES strains lack them. ▪ Other encapsulated bacteria include Klebsiella pneumoniae, Haemophilus influenzae, Bacillus anthracis, and Yersinia pestis.  Cell Wall Components  Certain bacterial cell wall substances HOW BACTERIAL enhance virulence: PATHOGENS ▪ M Protein: Found in Streptococcus pyogenes, aids in attachment and PENETRATE HOST resists phagocytosis. DEFENSES ▪ Opa Protein: Present in Neisseria gonorrhoeae, facilitates attachment and entry into host cells. ▪ Mycolic Acid: In Mycobacterium tuberculosis, helps resist digestion by phagocytes.  Enzymes  Bacteria produce extracellular HOW BACTERIAL enzymes (exoenzymes) that aid in PATHOGENS invasion: PENETRATE HOST ▪ Coagulases: Convert fibrinogen to DEFENSES fibrin, forming clots that protect bacteria from phagocytosis. ▪ Kinases: Break down fibrin clots (e.g., streptokinase). ▪ Hyaluronidase: Hydrolyzes hyaluronic acid, aiding tissue spread.  Enzymes  Bacteria produce extracellular HOW BACTERIAL enzymes (exoenzymes) that aid in PATHOGENS invasion: PENETRATE HOST ▪ Collagenase: Breaks down collagen, DEFENSES facilitating spread of infections like gas gangrene. ▪ Some bacteria produce IgA proteases to destroy IgA antibodies, aiding adherence.  Penetration into the Host HOW BACTERIAL  Pathogens attach using adhesins, triggering host cell signals for entry: PATHOGENS ▪ Bacteria like Salmonella and E. coli use PENETRATE HOST invasins to rearrange actin filaments in DEFENSES host cells, leading to membrane ruffling and engulfment.  Once inside, some bacteria (e.g., Shigella, Listeria) can use actin for movement within and between cells.  Survival Inside Phagocytes  Certain pathogens can survive or HOW BACTERIAL replicate within phagocytes: PATHOGENS ▪ Examples include Coxiella PENETRATE HOST burnetii, which requires low pH DEFENSES for replication, and others that escape or inhibit phagosome- lysosome fusion (e.g., Mycobacterium tuberculosis, HIV).  Role of Biofilms  Biofilms enhance resistance to HOW BACTERIAL phagocytosis: PATHOGENS ▪ Phagocytes struggle to penetrate PENETRATE HOST the extracellular polymeric DEFENSES substance (EPS) of biofilms. ▪ EPS may shield bacterial antigens from immune recognition and can even kill phagocytes (e.g., in Pseudomonas aeruginosa).  Using the Host’s Nutrients: Siderophores HOW  Iron Requirement: Most pathogenic MICROORGANISMS bacteria require iron for growth, but DAMAGE HOST free iron levels in the human body are low. CELLS  Siderophores:  Proteins secreted by bacteria to bind and sequester iron from host iron-transport proteins (e.g., transferrin, lactoferrin).  Damage Mechanisms Microorganisms can damage host HOW cells through four primary mechanisms: MICROORGANISMS 1. Using the host's nutrients. DAMAGE HOST CELLS 2. Causing direct damage at the site of invasion. 3. Producing toxins that affect distant sites. 4. Inducing hypersensitivity reactions.  Using the Host’s Nutrients: Siderophores HOW  Siderophores: MICROORGANISMS  The iron-siderophore complex is DAMAGE HOST taken up by bacterial receptors, CELLS allowing bacteria to acquire essential iron.  Some pathogens can also directly bind to and internalize iron-transport proteins.  Direct Damage HOW MICROORGANISMS  Pathogens can cause direct damage DAMAGE HOST as they metabolize within host cells: CELLS ▪ Cell Rupture: Pathogen multiplication often leads to cell lysis, releasing more pathogens into surrounding tissues.  Direct Damage  Pathogens can cause direct damage HOW as they metabolize within host cells: MICROORGANISMS ▪ Induction of Phagocytosis: DAMAGE HOST Certain bacteria (e.g., E. coli, CELLS Shigella) can induce host cells to engulf them, causing disruption and eventual cell death.  Pathogens may also penetrate host cells using enzymes or motility, leading to further cellular damage.  Direct Damage  Pathogens can cause direct damage HOW as they metabolize within host cells: MICROORGANISMS ▪ Induction of Phagocytosis: DAMAGE HOST Certain bacteria (e.g., E. coli, CELLS Shigella) can induce host cells to engulf them, causing disruption and eventual cell death.  Pathogens may also penetrate host cells using enzymes or motility, leading to further cellular damage. HOW Production of Toxins MICROORGANISMS  Toxins are poisonous substances DAMAGE HOST produced by microorganisms, often CELLS key to their pathogenicity. ▪ Toxigenicity refers to the ability of a microbe to produce toxins.  Types of Toxins  Exotoxins: ▪ Secreted by bacteria (mostly gram- HOW negative) during growth; can be MICROORGANISMS proteins or enzymes. DAMAGE HOST ▪ Highly potent; even small amounts can cause significant harm (e.g., botulinum CELLS toxin). ▪ Specific effects on host tissues; examples include neurotoxins (affecting nerves) and enterotoxins (affecting the gastrointestinal tract). ▪ Can be inactivated for vaccine development (toxoids).  Types of Toxins  Endotoxins: HOW ▪ Part of the outer membrane of gram- negative bacteria; specifically, the lipid MICROORGANISMS A component of lipopolysaccharides DAMAGE HOST (LPS). CELLS ▪ Released upon bacterial death or lysis; cause systemic effects like fever and shock. ▪ Induce cytokine release from macrophages, leading to toxic effects at high concentrations.  Exotoxin Types 1. A-B Toxins: Composed of two HOW polypeptide parts (A for activity, B for binding). Example: diphtheria toxin. MICROORGANISMS 2. Membrane-Disrupting Toxins: Lyse host DAMAGE HOST cells by disrupting plasma membranes; CELLS examples include leukocidins and hemolysins. 3. Superantigens: Stimulate excessive immune responses by activating T cells nonspecifically, leading to severe symptoms like shock.  Endotoxin Effects HOW  Common symptoms include chills, MICROORGANISMS fever, weakness, and potentially DAMAGE HOST septic shock due to increased CELLS capillary permeability and fluid loss.  Endotoxins do not promote effective antitoxin formation.  Plasmids and Pathogenicity HOW  Plasmids: Circular DNA molecules MICROORGANISMS that can carry genes for virulence DAMAGE HOST factors (e.g., toxins, adhesins). CELLS  Lysogeny: Some bacteriophages integrate their DNA into bacterial genomes, leading to new pathogenic traits in lysogenic bacteria.  Access to Host: Viruses must gain entry into a host organism. PATHOGENIC Evasion of Immune Defenses: PROPERTIES OF Successful viruses evade the host's VIRUSES immune system. Cell Damage: Viruses cause damage or death to host cells while replicating.  Mechanisms for Evading Host Defenses PATHOGENIC  Intracellular Growth: Viruses can PROPERTIES OF replicate inside host cells, inaccessible VIRUSES to immune components.  Attachment Sites: Viruses possess specific sites that bind to receptors on target cells, facilitating entry. ▪ Example: Rabies virus mimics acetylcholine to enter cells.  Mechanisms for Evading Host Defenses PATHOGENIC  HIV Evasion PROPERTIES OF ▪ Hides attachment sites from VIRUSES immune detection. ▪ Targets CD4 proteins on T lymphocytes, making it difficult for antibodies to neutralize the virus.  Cytopathic Effects (CPE) of Viruses PATHOGENIC  Cell Death: Viral infections typically PROPERTIES OF lead to host cell death via: VIRUSES ▪ Accumulation of viruses. ▪ Disruption of cellular functions (e.g., DNA/RNA/protein synthesis).  Cytopathic Effects (CPE) of PATHOGENIC Viruses PROPERTIES OF  Types of CPE: VIRUSES ▪ Cytocidal Effects: Directly result in cell death. ▪ Noncytocidal Effects: Cause damage without killing the cell.  Specific Cytopathic Effects PATHOGENIC 1. Inhibition of Macromolecular PROPERTIES OF Synthesis: Some viruses halt VIRUSES cellular processes, e.g., Simplexvirus stops mitosis. 2. Lysosomal Enzyme Release: Host cell lysosomes release enzymes, leading to cell destruction.  Specific Cytopathic Effects 3. Inclusion Bodies Formation: Viral PATHOGENIC components aggregate in infected PROPERTIES OF cells, aiding in diagnosis (e.g., VIRUSES Negri bodies in rabies). 4. Syncytium Formation: Infected cells may fuse to form large multinucleate cells seen in measles and mumps.  Specific Cytopathic Effects 5. Functional Changes Without PATHOGENIC Visible Damage: Example includes PROPERTIES OF measles virus reducing IL-12 VIRUSES production, impairing immune response. 6. Antigenic Changes on Cell Surfaces: Viral proteins alter host cell antigens, prompting immune targeting.  Specific Cytopathic Effects 7. Chromosomal Damage: Some PATHOGENIC viruses induce chromosomal PROPERTIES OF breakage or activate oncogenes, VIRUSES leading to cancer risks. 8. Cell Transformation: Certain viruses can transform host cells into abnormal growth patterns, losing contact inhibition.  Interferon Production  Infected cells produce alpha and beta interferons to protect neighboring PATHOGENIC uninfected cells: PROPERTIES OF ▪ Inhibit viral and host protein VIRUSES synthesis. ▪ Induce apoptosis in infected cells.  Many viruses have evolved mechanisms to evade interferon responses, hindering their effectiveness.  Fungi  Pathogenic Mechanisms: PATHOGENIC ▪ Toxins: PROPERTIES OF  Trichothecenes: Inhibit protein FUNGI, PROTOZOA, synthesis; cause headaches, chills, HELMINTHS, AND nausea (produced by Fusarium ALGAE and Stachybotrys).  Ergotism: Caused by Claviceps purpurea, leading to hallucinations and gangrene due to blood circulation issues.  Fungi  Virulence Factors: PATHOGENIC PROPERTIES OF ▪ Some fungi secrete proteases that FUNGI, PROTOZOA, modify host cell membranes for HELMINTHS, AND attachment. ALGAE ▪ Cryptococcus neoformans produces a capsule that resists phagocytosis. ▪ Resistance to antifungal drugs can occur through decreased receptor synthesis. PATHOGENIC PROPERTIES OF Protozoa FUNGI, PROTOZOA,  General Characteristics: HELMINTHS, AND ▪ Protozoa can cause disease through ALGAE their presence and metabolic waste products.  Protozoa  Pathogenic Mechanisms: PATHOGENIC ▪ Cell Invasion: PROPERTIES OF FUNGI, PROTOZOA, ▪ Plasmodium invades red blood HELMINTHS, AND cells, causing them to rupture. ALGAE ▪ Toxoplasma prevents normal digestion within macrophages, allowing it to grow. ▪ Giardia intestinalis attaches to host cells and digests tissue fluids. PATHOGENIC Protozoa PROPERTIES OF FUNGI, PROTOZOA,  Evasion of Host Defenses: HELMINTHS, AND ▪ Some protozoa use antigenic ALGAE variation to evade the immune system (e.g., Trypanosoma changes its surface antigens). PATHOGENIC PROPERTIES OF Helminths FUNGI, PROTOZOA,  General Characteristics: HELMINTHS, AND ▪ Helminths can produce disease ALGAE symptoms through tissue damage or large parasitic masses.  Helminths PATHOGENIC  Pathogenic Mechanisms: PROPERTIES OF ▪ Example: Wuchereria bancrofti FUNGI, PROTOZOA, causes elephantiasis by blocking HELMINTHS, AND lymphatic circulation, leading to ALGAE severe swelling. ▪ Waste products from helminths can also contribute to disease symptoms. PATHOGENIC PROPERTIES OF Algae FUNGI, PROTOZOA,  General Characteristics: HELMINTHS, AND ALGAE ▪ Some algae produce neurotoxins that affect human health.  Algae PATHOGENIC  Pathogenic Mechanisms: PROPERTIES OF ▪ Saxitoxin: Produced by dinoflagellates FUNGI, PROTOZOA, (e.g., Alexandrium), causes paralytic HELMINTHS, AND shellfish poisoning in humans who ALGAE consume contaminated mollusks. ▪ Domoic Acid: Produced by diatoms (Pseudo-nitzschia), can lead to amnesic shellfish poisoning, causing memory loss or death.   Portals of exit are specific routes through which pathogens leave the body, typically through secretions, excretions, or shed tissue. PORTALS OF EXIT  Microbes often use the same portal for both entry and exit, correlating with the infected area of the body.  Understanding portals of exit is crucial for epidemiologists in tracking and controlling disease spread.  Common Portals of Exit  Respiratory Tract ▪ Pathogens exit through mouth and PORTALS OF EXIT nose discharges during coughing or sneezing. ▪ Diseases include tuberculosis, whooping cough, pneumonia, scarlet fever, meningococcal meningitis, chickenpox, measles, mumps, smallpox, and influenza.  Common Portals of Exit  Gastrointestinal Tract ▪ Pathogens are expelled in feces or PORTALS OF EXIT saliva. ▪ Associated diseases include salmonellosis, cholera, typhoid fever, shigellosis, amebic dysentery, poliomyelitis (via feces), and rabies, mumps, infectious mononucleosis (via saliva).  Common Portals of Exit  Genitourinary Tract PORTALS OF EXIT ▪ Microbes are found in secretions from the penis and vagina. ▪ Urine can carry pathogens responsible for typhoid fever and brucellosis.  Common Portals of Exit  Transmission via Blood ▪ Infected blood can be transmitted by PORTALS OF EXIT biting insects or contaminated needles/syringes. ▪ Diseases transmitted this way include yellow fever, plague, tularemia, malaria (by insects), and AIDS and hepatitis B (by needles/syringes).