Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Chapter 15 Microbial Mechanisms of Pathogenicity Microbial Mechanisms of Pathogenicity • Pathogenicity: the ability to cause disease • Virulence: the degree or extent of pathogenicity • Disease is caused by the microbe overpowering the host’s defense (immune response) – Due to microbes directly damages host tissue – Due to accumulation of microbial waste products How Microorganisms Enter a Host • Portals of entry: the avenue by which a pathogen gains access to the body – Mucous membranes penetrate membrane lining; Most pathogens enter through the mucous membranes of the gastrointestinal and respiratory tracts • respiratory tract: by inhalation (easiest and most commonly used route) • gastrointestinal tract: by food, water and contaminated fingers • genitourinary tract: sexually • conjunctiva: birth canal, contact lenses, hands/fingers How Microorganisms Enter a Host – Skin through hair follicles and sweat gland ducts; intact skin is the first line of defense; most microorganisms cannot penetrate intact skin – Parenteral route: direct deposition into tissues beneath the skin and mucous membranes by punctures, injections, bites, cuts, wounds, surgery and splitting • Many pathogens have a preferred portal of entry entry through other portal may not cause disease Numbers of invading microbes • ID50: Infectious dose for 50% of the test population – Used to compare the relative virulence of a microbe under experimental conditions – e.g. Bacillus anthracis (can cause infection via 3 different portals of entry Portal of entry Skin (cutaneous anthrax) ID50 10-50 endospores Inhalation (inhalation anthrax) 10,000-20,000 endospores Ingestion (gastrointestinal anthrax) 250,000-1,000,000 endospores Numbers of invading microbes • LD50: Lethal dose (of a toxin) for 50% of the test population – Used to express the potency of a toxin – e.g. LD50 in mice botulinum toxin 0.03 ng/kg Shiga toxin 250 ng/kg staphylococcal enterotoxin 1,350 ng/kg Adherence (Attachment) • Adhesins/ligands bind to complementary surface receptors on host cells • Host cell receptors are typically sugars (e.g. mannose) • Majority of adhesins on the microorganisms are glycoproteins or lipoproteins – Glycocalyx – Fimbriae – M protein Streptococcus mutans Escherichia coli Streptococcus pyogenes Adherence (Attachment) – Opa protein – Tapered end Neisseria gonorrhoeae Treponema pallidum • Biofilms: a microbial community that usually forms a slime layer on a surface – Mass of microbes attach to living and nonliving surfaces by their extracellular products (e.g. glycocalyx) – e.g. Dental plaque, scum on shower doors, contact lenses, heart valves, medical catheters – Resist disinfectants and antibiotics How Bacterial Pathogens Penetrate Host Defenses • Capsule increases the virulence by resisting the phagocytosis – e.g. Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, and Bacillus anthracis – Host’s defense: antibodies produced against capsules allows encapsulated bacteria to be destroyed by phagocytosis How Bacterial Pathogens Penetrate Host Defenses • M proteins (on cell surface and fimbriae) mediates attachment and helps resist phagocytosis – Host’s defense: antibodies against M proteins • Waxes in the cell wall of Mycobacterium tuberculosis resist digestion by phagocytes; bacteria can even multiply inside phagocytes How Bacterial Pathogens Penetrate Host Defenses • Extracellular (exoenzymes) enzymes aid virulence – Coagulase coagulate (clot) fibrinogen in blood; fibrin clot may protect the bacterium from phagocytosis and isolate bacteria from other defenses of the host – Kinases digest/dissolve fibrin clots; allows bacteria to spread from a localized area How Bacterial Pathogens Penetrate Host Defenses – Hyaluronidase hydrolyses hyaluronic acid; cause the tissue blackening of infected wounds and allows bacteria to spread from the initial site of infection – Collagenase hydrolyzes collagen; helps bacteria to spread – IgA proteases destroy IgA antibodies; remove protection on mucosal surfaces How Bacterial Pathogens Penetrate Host Defenses • Antigenic variation: alter surface proteins (antigens) to escape antibodies (can inactivate or destroy antigens) – activating alternative genes (e.g. Opa protein) • Penetration into the host cell cytoskeleton – Use host’s cytoskeleton (actin) to move through the host cytoplasm and between host cells (e.g. Shigella species and Listeria species) – Invasins: cause formation of an actin basket around Salmonella and move bacteria into the cell Penetration into the Host Cell Figure 15.2 How Bacterial Pathogens Damage Host Cells • If phagocytes can eliminate invading microorganisms, no further damage is done. • If pathogens overcome the host defense damage to the host cells – Use the host’s nutrients – Cause direct damage at the site of infection – Produce toxins (cause damage in other parts of the body) – Induce hypersensitivity reactions Using the host’s nutrient • Iron (required for most pathogens’ growth) – Some produce siderophores secreted by bacteria to take iron from host iron-transport proteins – Some have receptors that bind directly to irontransport proteins and hemoglobin – Some produce toxins kill the host cells to obtain iron from dead host cells Direct damage • Pathogens cause damage by rupturing the host cells as they metabolize and multiply inside cells – Use host cell for nutrients and produce waste – As the host cells rupture, pathogens are released and free to spread infections • Most damage is done by production of toxins Production of toxins • Toxin: poisonous substances that contribute to pathogenicity – Exotoxins (many are encoded by plasmids or lysogenic conversion) and endotoxins • Toxigenicity: ability to produce a toxin • Toxemia : presence of toxin in the host's blood • Toxoid: inactivated toxin used in a vaccine (e.g. diphtheria and tetanus vaccine) • Antitoxin: antibodies against a specific toxin; provide immunity to exotoxins Exotoxins • Proteins (many are enzymes can be used over and over again) • Most of the genes are carried on bacterial plasmids or phages • Soluble in body fluids rapidly diffuse and transport throughout the body Figure 15.4a Exotoxin • Only need minute amount to cause diseases; among the most lethal substances known – Signs and symptoms of the disease is caused by exotoxin, not by bacteria • Can induce formation of antitoxins • Three principal types of exotoxins (based on structure and function) – A-B toxins or type III toxins – Membrane-disrupting toxins or type II toxins – superantigens or type I toxins Exotoxins • A-B toxins (type III toxins) – Majority of exotoxins in this category – 2 parts: A is the active (enzyme) component & B is the binding component Figure 15.5 Exotoxins • Membrane-disrupting toxins or type II toxins – Lyse host’s cells by: • Making protein channels in the plasma membrane (e.g. hemolysins and leukocidins) – hemolysins: form protein channels to destroy erythrocyte (staphylococci and streptococci) • Disrupting phospholipid bilayer – Contribute to virulence by killing host immune cells (phagocytic cells) and aid bacteria to escape from phagosomes into the host’s cytoplasm • e.g. Leukocidins (kill phagocytic leukocytes and macrophages by forming protein channels) Exotoxins • Superantigens or type I toxins – Bacterial proteins (e.g. staphylococcus toxins which cause food poisoning & toxic shock syndrome) – Cause an intense immune response to release cytokines from host T cells (nonspecific stimulation of T cells causing proliferation and release massive amount of cytokines) – Excessively high levels of cytokines (small protein hormones) enter the bloodstream to cause fever, nausea, vomiting, diarrhea, shock, and even death Exotoxins • Neurotoxins: attaches to nerve cells and interferes with normal nerve impulse conduction • Cytotoxins: attaches to wide variety of cells and either kills host cells or alters their function – Erythrogenic toxins: damage the plasma membrane of blood capillaries under the skin and produce a red skin rash (e.g. Streptococcus pyogenes) • Enterotoxins: attaches to the lining of the gastrointestinal tract and cause gastroenteritis Exotoxins Exotoxin Lysogenic conversion A-B toxin. Inhibits protein synthesis. + • Streptococcus pyogenes Membrane-disrupting. Erythrogenic. + • Clostridium botulinum A-B toxin. Neurotoxin + • C. tetani A-B toxin. Neurotoxin • Vibrio cholerae A-B toxin. Enterotoxin • Corynebacterium diphtheriae • Staphylococcus aureus Superantigen. Enterotoxin. + Endotoxin = Lipid A Figure 15.4b Bacterial Cell Wall Fig. 4.13 b & c Endotoxins • Lipopolysaccharides (Lipid A portion) • Released when gram-negative bacteria die and their cell walls lyse – Antibiotics can lyse the bacterial cells to release endotoxins – Endotoxins also released during bacterial replication • Salmonella typhi, Proteus spp., and Neisseria miningitidis Endotoxins • All endotoxins produce the same sings and symptoms; however not to the same degree – – – – Chills, fever, weakness, generalized aches In some cases, shock and even death Can also cause miscarriage Activate blood-clotting proteins cut off or reduce blood supply death of tissues = disseminated intravascular clotting • Stimulate macrophages to release cytokines in very high concentrations (toxic level) – IL-1 and TNF Endotoxins • Fever (pyrogenic response) Figure 15.6 – Aspiring & acetaminophen reduce fever by blocking the synthesis of prostaglandins Endotoxins • Shock: any life-threatening loss of blood pressure – Septic shock: shock caused by bacteria – Endotoxic shock: shock caused by gram-negatives • Release of tumor necrosis factor (TNF) or cachectin by phagocytes (after ingesting gramnegative bacteria) into the bloodstream TNF damage blood capillaries drop in blood pressure septic shock Endotoxins • Do not induce effective antitoxins formation – Antibodies are produced, but tend not to counter the effect of the toxin • Endotoxins are more stable at high heat than exotoxins • Limulus amoebocyte lysate (LAL) assay used to detect presence of endotoxin in drugs, medical devices, and body fluids Plasmids, lysogeny, and pathogenicity • Plasmids carry genes for antibiotic resistance (R factors) & information for pathogenicity (virulence factors) – Encode for toxins, capsules, and fimbriae • Prophage (lysogeny) lysogenic conversion – Immune to infection by the same type of phage – Increase pathogenicity (genes for toxins, capsules) – Increase number of pathogenic bacteria (horizontal transfer) Pathogenic Properties of Viruses • Mechanism for evading host defenses – Penetrate and grow inside host cells to evade the reach of components of the immune system – Gain access to the potential host cells using attachment sites (on virus) specific to receptors on the potential host cells • Sometimes, attachment sites mimic substances useful to the host cells – Hide attachment sites from the immune response + attack components of the immune system directly (e.g. HIV virus) Pathogenic Properties of Viruses • Cytopathic effects (CPE) of viruses: visible effects of viral infection – Cytocidal effects: result in cell death – Noncytocidal effects: result in cell damage but not cell death – Stop synthesis of macromolecules in the host; stop mitosis; loss of contact inhibition – Formation of inclusion bodies; syncytium – Induce production of interferons in infected cells; antigenic changes on the surface of the infected cells; chromosomal changes in the infected cells; transformation Cytopathic Effects of Viruses Table 15.4 Pathogenic Properties of Fungi • No well-defined set of virulence factors • Fungal waste products (toxins) may cause symptoms – Tichothecene toxins inhibit protein synthesis (e.g. Fusarium) – Ergot toxin = hallucinogen (e.g. Claviceps) – Aflatoxin (e.g. Aspergillus) is carcinogenic – Mycotoxins (neurotoxins such as phalloidin & amanitin, produced by Amanita) may be lethal if ingested Pathogenic Properties of Fungi • Chronic infections provoke an allergic response • Some have Virulence factors such as proteases (e.g. Candida, Trichophyton) – Allow attachment of the fungi by modifying host cell membranes • Capsule prevents phagocytosis (e.g. Cryptococcus) • Decrease synthesis of receptors for antifungal drugs & become resistant to the drugs Pathogenic Properties of Protozoa • Presence of protozoa & protozoan waste products may cause symptoms • Avoid host defenses by – Growing in phagocytes (e.g. Plasmodium & Toxoplasma) – Antigenic variation (e.g. Trypanosoma) • Attach and digest the host cells and tissue fluids (e.g. Giardia) Pathogenic Properties of Helminths and Algae • Presence of parasite (helminth) interferes with host function • Parasite's metabolic waste can cause symptoms • Use host tissues for their growth cellular damage (cause symptoms) • Few species of algae (dinoflagellates) produce neurotoxins – e.g. Saxitoxin cause paralytic shellfish poisoning Portals of Exit • Microbes leave the body through specific routes to spread infections generally a microbe uses the same portal for entry and exit – Respiratory tract (most common portal of exit) via mouth and nose by coughing or sneezing – Gastrointestinal tract (most common portal of exit) via feces or saliva – Genitourinary tract via secretions from the penis and vagina (for sexually transmitted diseases) or urine Portals of Exit – Skin or wound infections via shedding, contact, or drainage from wounds – Infected blood via biting arthropods, needles/syringes Mechanisms of Pathogenicity Figure 15.9 Chapter Review Figure 15.9 Chapter Review 1. Know different portals of entry and exit, and how they enter or leave a host – Generally a microbe uses the same portal for entry and exit • – respiratory and gastrointestinal tracts = most common portal of entry and exit Mucous membranes • • • respiratory tract – enter by inhalation; exit by mouth and nose through coughing or sneezing gastrointestinal tract – enter by food, water, and contaminated fingers; exit by feces or saliva genitourinary tract – transmitted sexually; exit through secretions from the penis and vagina (for STDs) or urine Chapter Review – Skin cannot penetrate unbroken skin; enter through hair follicles and sweat gland ducts; exit through shedding, contact (e.g. sweat) – Parenteral route: direct deposition into tissues beneath the skin and mucous membranes by punctures, injections, bites, cuts, wounds, surgery and splitting; if there is wound infection, exit through drainage from wounds, blood-borne pathogen exit through biting arthropods or needles/syringes – Many pathogens have a preferred portal of entry; if enter through different portal, may not cause disease Chapter Review 2. Know how pathogens adhere or attach to a susceptible host – Pathogens use adhesins or ligands to bind to complementary surface receptors on host cells – E.g. of adhesins/ligands: glycocalyx (Streptococcus mutans); fimbriae (Escherichia coli); M protein (Streptococcus pyogenes); Opa protein (Neisseria gonorrhoeae) – Pathogens can also use biofilms to adhere (mass of bacteria secrete glycocalyx) to living and nonliving surface; biofilms resist disinfectants and antibiotics Chapter Review • • Biofilms: a microbial community that usually forms a slime layer on a surface e.g. Dental plaque, scum on shower doors, contact lenses, heart valves, medical catheters 3. Know how pathogens penetrate or evade host defenses – Capsule formation: resist phagocytosys host antibodies produced against capsules allow encapsulated bacteria to be destroyed by phagocytosis Chapter Review – Cell wall components (contain chemical substances) contribute to virulence • M proteins: mediates attachment and helps resist phagocytosis antibodies produced against M protein by host allows bacteria to be destroyed • Waxes in the cell wall of Mycobacterium: resist digestion by phagocytes; bacteria can even multiply inside phagocytes tend to become a chronic disease – Extracellular enzymes (exoenzymes) aid in virulence • protect the bacterium by forming a protective clot to avoid phagocytosis and other host’s defenses Coagulase Chapter Review • Allows bacterium to spread from the initial site of infection kinases, hyaluronidase & collagenase • Remove protection on mucosal surfaces IgA proteases – Antigenic variation: escape inactivation or destruction by host’s antibodies – Penetration into the host cell cytoskeleton • Invasins (Salmonella bacteria) to carry bacteria into the cell • Use host’s cytoskeleton to move through the host cytoplasm and between host cells (Shigella species and Listeria species) Chapter Review 4. Know how bacteria pathogens can damage host cells – Cause direct damage at the site of infection by rupturing the host cells as they metabolize and multiply Release from the host allows spread of infections – Production of toxins cause the most damage to a host (cause damage in other parts of the body) • Many of the exotoxins (proteins; many are enzymes) are encoded by plasmids or lysogenic conversion • Endotoxins are part of gram-negative cell wall (Lipid A) Chapter Review – Carrying plasmids allow bacteria to become antibiotic resistant; increase pathogenicity (carry virulence factors such as genes for toxins, capsule, and fimbriae) – Lysogenic conversion: prophage carry genes for toxins & capsules to increase pathogenicity; increase number of pathogenic bacteria (horizontal transfer) Chapter Review 5. Know pathogenic properties of viruses – Viruses can cause cytocidal effects (kill host cells) or noncytocidal effects (result in cell damage, not cell death) – Mechanisms for evading host defenses • Evade the host’s immune response by growing intracellularly • Gain access to the host cells using attachment sites (on virus) to bind to specific receptors (on hosts) • Hide attachment sites (on virus) from the immune response or attack components of the immune system directly Chapter Review 6. Know pathogenic properties of fungi, protozoa, helminths, and algae – fungi toxins (e.g. aflatoxin & mycotoxins); capsules; chronic infections cause allergic response; some become resistant to antifungal drugs by decreasing synthesis of receptors for the drugs – Protozoa avoid host defense by growing inside phagocytes; antigenic variation; damage to host tissues; metabolic waste Chapter Review – Helminth metabolic waste; cellular damage (tissue damage) – Algae (dinoflagellates) neurotoxins 7. Know these terms: pathogenicity, virulence, toxigenicity, toxoid, antitoxin, septic shock