Microbial Mechanisms of Pathogenicity PDF

MICROBIAL MECHANISMS OF PATHOGENICITY  Introduction of Bacterial Pathogenesis 1. Infection - growth and multiplication of a microbe in or on the body with or without the production of disease 2. Disease - abnormal state in which all or part of the body is not functioning properly...

MICROBIAL MECHANISMS OF PATHOGENICITY  Introduction of Bacterial Pathogenesis 1. Infection - growth and multiplication of a microbe in or on the body with or without the production of disease 2. Disease - abnormal state in which all or part of the body is not functioning properly 3. Pathogenicity - The ability/capacity of a bacterium to cause disease 4. Virulence - is the measure of the pathogenicity of a microorganism. 5. Pathogenesis - refers both to the mechanism of infection and to the mechanism by which disease develops.  Virulence Factors of Infectious Disease Virulence – degree of pathogenicity – Virulence factors contribute to an organism’s virulence Adhesion factors Biofilms Extracellular enzymes Toxins Antiphagocytic factors  Terms – Pathogen: disease causing organism – Pathology: scientific study of disease – Etiology: causative agent of a disease – Host: organism that shelters and supports the growth of pathogenic organisms  Strict pathogens - are more virulent and can cause diseases in a normal person. Opportunistic pathogens - are typically members of normal flora and cause diseases when they are introduced into unprotected sites, usually occur in people with underlying conditions. Mechanisms of Pathogenicity  Portals of Entry Pathogens – Must gain access to host – Adhere to host tissue – Penetrate or evade host defenses – Damage host tissue  Portals of Entry Portal of Entry – Routes microorganisms can penetrate the body 1- mucous membranes 2- skin 3- parenteral route 4- preferred portal of entry  1. Mucous membrane entry Mucous membranes – Respiratory tract Easiest and most frequent route of infection Inhaled through nose or oral cavity Duct particles, moisture droplets Common cold, pneumonia, tuberculosis, influenza and smallpox  Mucous Membrane Entry Mucous membrane – Gastrointestinal route In food or water Contaminated fingers Most are inactivated by stomach acid, enzymes, bile Poliomyelitis, hepatitis A, amoeboid dysentery, cholera  Mucous Membrane Entry Mucous membrane – Genitourinary tract Contracted sexually Intact or broken mucous membranes STI (sexually transmitted infections) HIV, genital warts, genital herpes, syphilis, and gonorrhea  2. Skin Skin – Unbroken skin – barrier to microorganisms – Hair follicles and sweat gland ducts – Some pathogens penetrate normal skin Hookworm larva – Some pathogens grow on keratin of skin Ringworm – Abscesses, burns  3. Parenteral Route Parenteral route – Microorganisms deposited directly below skin – Puncture wounds, injections, bites, wounds, and surgery – Tetanus, rabies, hepatitis B, and malaria  4. Preferred Portal of entry Some organisms must enter via preferred route to cause disease Some organisms may cause disease with many different route of entry Preferred Portal of Entry  NUMBERS OF INVADING MICROBES The virulence of a microbe or the potency of its toxin is often expressed as the LD50. LD50(lethal dose for 50% of hosts) amount of toxin or pathogen necessary to kill 50% of the population in a particular time frame. ID50:(infectious dose for 50% of hosts) is the dose required to produce a demonstrable infection in 50% of the test animals.  Numbers of Invading Microbes LD50 – lethal dose for 50% of a sample population – Measures potency of toxins – LD50 Botulinum toxin = 0.03 ng/kg Shiga toxin = 250 ng/kg Staphylococcal enterotoxin = 1350 ng/kg Numbers of Invading Organisms Disease more likely with more organisms (pathogens) ID50- infectious dose for 50% of a sample population – Measures virulence of a microorganism – Anthrax Cutaneous (skin) ID50 10-50 endospores Inhalation ID50 10,000-20,000 endospores Gastrointestinal ID50 250,000 – 1,000,000 endospores  Adherence of microorganisms Microorganisms after entry into host must adhere to host Adherence – Attachment of microorganisms after entry to host – Surface molecules Ligands and adhesins bind specifically for receptors on host cells. Glycocalyx, pili, fimbriae, flagella Adherence Adherence Figure 15.1 Adherence Figure 15.1 Adherence Figure 15.1  Adherence Receptors of host cells – Usually, a sugar i.e., mannose Altering receptor, adhesin, or both alters ability for infection to occur  Adherence Examples – Streptococcus mutans attaches to teeth by its glycocalyx – Actinomyces have fimbriae that adhere to glycocalyx of S. mutans – Involved in dental caries (cavities) – E. coli have adhesins on fimbriae, attach to specific regions of small intestine  Biofilms Biofilms – Communities of microorganisms and their extracellular products that attach to non-living and living surfaces – biofilm is resistant to disinfectants and antibiotics Algae Dental plaque Medical catheters  Mechanisms which assist bacterial survival in the host O antigen polysaccharide chain Capsular antigen Capsule production M protein production Production of Fc-binding proteins  Mechanisms which assist bacterial survival in the host Production of leukotoxins Interference with phagosome-lysosome fusion Resistance to oxidative damage Antigenic mimicry of host antigens Antigenic variation of surface antigens Coagulase production  How pathogens penetrate host defenses Capsules – Impair phagocytosis Prevents phagocytic cell from attaching to microorganism – Made of glycocalyx – Streptococcus pneumoniae Griffith’s experiment of genetic transformation  How pathogens penetrate host defenses Components of Cell Wall – M – protein Mediates attachment to epithelium Resists phagocytosis – Opa (Opacity-Associated) Outer membrane protein – encoded by Opa genes Helps in attachment – Waxes (mycolic acid) Resist digestion by phagocytes Mycobacterium  Cell Wall Components – M protein resists phagocytosis § Streptococcus pyogenes – Opa protein inhibits T helper cells § Neisseria gonorrheae – Mycolic acid (waxy lipid) resists digestion § Mycobacterium tuberculosis  How pathogens penetrate host defenses Enzymes – Extracellular enzymes (exoenzymes) Dissolve material between cells, form or dissolve clots – Coagulase Converts fibrinogen to fibrin clot Isolates microorganism from host defenses Blood clots protect bacteria from phagocytosis from WBC’s and other host defenses Staphylococci - are often coagulase positive – boils – abscesses – Kinases Break down fibrin (Streptokinase - Streptococci ; Staphylokinase - Staphylococci  – Hyaluronidase Breaks down cell to cell adhesions in connective tissue (Breaks down Hyaluronic acid (found in connective tissues) “Spreading Factor” mixed with a drug to help spread the drug thru a body tissue – Collagenase Produced by several Clostridium perfringens - Gas Gangrene – uses this to spread thru muscle tissue Breaks down protein collagen (found in many connective tissues) – IgA proteases Destroy antibodies Necrotizing Factor - causes death (necrosis) to tissue cells “Flesh Eating Bacteria” Necrotizing fasciitis  How pathogens penetrate host defenses Antigenic variation – Pathogens alter surface proteins Several versions of Opa protein – New antibodies must be produced Gonorrhea Sleeping sickness Influenza  How pathogens penetrate host defenses Penetration into host cells cytoskeleton – Invasins Rearrange actin filaments Facilitates movement of microorganism into cell How Pathogens Damage Host Cells 1- utilize host’s nutrients 2- direct damage in immediate vicinity of infection 3- toxin production  How pathogens penetrate host defenses Using host’s nutrients – Siderophores Bind iron away from host’s iron binding proteins Direct Damage – Multiplication of microorganism within cell Viruses Bacterial Protozoal  The Production of Toxins Toxin: Substance that contributes to pathogenicity; Poisonous compound produced by microorganisms Toxigenicity: Ability of a microorganism to produce a toxin Toxemia: Presence of toxin in the host's blood Toxoid: Inactivated toxin used in a vaccine Antitoxin: Antibodies against a specific toxin  Toxins Toxins – Fever – Cardiovascular abnormalities – Diarrhea – Shock – Destroy blood cells – Destroy blood vessels – Disrupt nervous system 2 types: exotoxins and endotoxins Exotoxins and Endotoxins Figure 15.4 Endotoxins vs. Exotoxins Exotoxins  Exotoxins Specific for a structure or function in host cell Figure 15.4a  Exotoxins usually are: 1. Synthesized by specific bacteria that often have plasmids or prophages bearing the exotoxin genes 2. Heat-labile proteins inactivated at 60 to 80°C 3. Among the most lethal substances known (toxic in very small doses [microgram per kilogram amounts]; e.g., the botulinum toxin) 4. Associated with specific diseases and have specific mechanisms of action 5. Highly immunogenic and stimulate the production of neutralizing antibodies called antitoxins 6. Easily inactivated by formaldehyde, iodine, and other chemicals to form immunogenic toxoids 7. Unable to produce a fever in the host directly 8. Often given the name of the disease they produce (e.g., the diphtheria toxin)  EXOTOXINS Produced inside some bacteria as part of their growth and metabolism and released into the surrounding medium. Are proteins, and many are enzymes. Most bacteria that produce exotoxins are gram-positive. The genes for most exotoxins are carried on bacterial plasmids or phages.  EXOTOXINS Are soluble in body fluids, so can easily diffuse into the blood and are rapidly transported throughout the body. Work by destroying particular parts of the host’s cells or by inhibiting certain metabolic functions.  Exotoxins 3 types of exotoxins 1. A-B Toxins Also called type III toxins Most exotoxins fall into this category A component – Active enzyme component B component – Binding component  Exotoxins A-B toxins – A-B toxin released by bacteria – A component inhibits protein synthesis and kills cell – B part binds to receptor of host cell – Toxin transported across membrane into cell – A-B components separate  Exotoxins Exotoxins 2. Membrane disrupting toxin Type II toxins Causes lysis of cells by disrupting cell membrane – Form protein channels » Staphylococcus aureus – Disrupt phospholipids » Clostridium perfringens Leukocidins – Membrane disrupting toxins that kill phagocytic WBC’s Hemolysins – Membrane disrupting toxins that kill erythrocyes RBC’s  Exotoxins 3. Superantigens Type I toxins Provoke intense immune response Protein in nature (antigens) Stimulate T – cells – Release cytokines (too much) » Causes fever, nausea, vomiting diarrhea  Exotoxins Neurotoxins – Attack nerve cells Target the nervous system, and can interfere with normal nerve impulse transmission, e.g., Clostridium tetani, Cl. botulinum. Cardiotoxins – Attack cardiac cells Hepatotoxins – Attack liver cells  Exotoxins Enterotoxins – Attack lining of GI tract Cytotoxin – Attacks wide variety of cells  Specific Exotoxins Diphtheria toxin – Cornybacterium diphtheriae – Requires lysogenic phage carrying tox gene – Cytotoxin inhibits protein synthesis in eukaryotic cells Erythrogenic toxins – Streptococcus pyogenes – A,B,C toxins damage plasma membranes of capillaries under skin causing rash Scarlet fever  Specific Exotoxins Botulinum toxin – Clostridium botulinum – Acts on neuromuscular junction – Prevents nerve impulse transmission Inhibits release of neurotransmitter acetylcholine Causes flaccid paralysis Tetanus toxin – Clostridium tetani – Tetanospasmin – CNS blocks inhibitory neurons to skeletal muscle – Results in uncontrollable muscle contractions – Lock jaw  Specific Exotoxins Vibrio enterotoxin – Vibrio cholerae – Produces cholera toxin – Sub unit B attaches to epithelium of intestinal tract – Sub unit A causes cells to secrete large amounts of electrolytes causing diarrhea  Specific Exotoxins Staphylococcal enterotoxin – Staphylococcus aureus – Similar to cholera toxin  Roles of Exotoxins in Disease Bacterial exotoxins affect a human host three main ways: (1) ingestion of preformed exotoxin (2) colonization of a mucosal surface followed by exotoxin production, and (3) colonization of a wound or abscess followed by local exotoxin production.  Endotoxins Endotoxins – Part of the outer membrane – Lipopolysaccharides (LPS) Lipid A – Released when gram (-ve) bacteria undergo lysis and multiplication  Endotoxins Endotoxins – Cause WBC to release cytokines Toxic at these levels – Cause chills, fever, weakness, generalized aches, shock and death – Can cause activation of blood clotting mechanisms causing tiny blood clots Disseminated intravascular coagulation (DIC) Endotoxins Endotoxins and the Pyrogenic Response Figure 15.6  Portals of Exit Routes that microbes use to exit host Three common methods: – Respiratory tract: via cough/sneeze – GI tract: via feces and saliva – Urogenital: via urine, vaginal/penile secretions – Skin: via open wounds – Blood: Biting arthropods, needles or syringes, surgery  Portals of Exit (Preferred Ways to Leave the Body and Spread Infection) Respiratory Tract (Coughing or Sneezing) Gastrointestinal Tract (Saliva or Feces) Urogenital Tract (Secretions from the Vagina or Penis) Arthropods and Syringes provide a portal of exit for microbes in blood.  Movement of Pathogen Out of Host Pathogens leave host through portals of exit  Pathogenic Properties of Viruses Cytopathic effects of viruses – Animal viruses usually cause death of host cell Accumulation of multiplying viruses Alter permeability of cell membrane Inhibit host DNA or RNA – Cytopathic effects (CPE) Visible effects of viral infection cytocidal or noncytocidal  CPE’s 1. Macromolecule synthesis halted – Mitosis inhibited (Herpes virus) 2. Release of lysosomes within cell - a destruction of cellular contents 3. Inclusion bodies – Viral parts, nucleic acids – Various size and staining characteristics Eosinophilic, basophilic – Negri bodies (Rabies)  CPE’s 4. Syncytium – Adjacent infected cells fuse 5. Changes in host cell functions 6. Cause the host cell to produce interferons 7. Antigenic changes on plasma membrane 8. Chromosomal changes in host cell and conversion of oncogenes 9. Transformation of host cell – Cause spindle shaped cells – Lack contact inhibition  Fungal pathogenic properties Secretion of enzymes – e.g., Proteases Capsules Toxins - mycotoxins Ergot Aflatoxin  Protozoal Pathogenic Properties Protozoal – Rupture of cells Malaria – Digest cells and tissue – Alter surface antigens 1,000 different antigens  Helminth Pathogenic Properties Utilize host tissue for growth and reproduction Produce large masses Waste products of helminths