Notes

Outline

Mechanisms of Microbial Pathogenicity

Definitions PATHOGENICITY -The ability to produce pathology VIRULENCE - The relative pathogenicity INFECTION - Host suffers an impairment of a normal function due to an organism that lives within or upon it

"Infectious diseases are associated with..." Infectious diseases are associated with organisms incapable of independent existence - Obligate parasites They only rarely produce diseases

"No organism can really be..." No organism can really be called nonpathogenic Animals reared in germ-free environments are susceptible to generalized infection by some of the common “nonpathogens”

"Virulence" Virulence Disease = Resistance                    (host or tissue)

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Organism with increased virulence

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"The “wandering”" The “wandering” of an organism from its usual habitat may result in disease due to lower resistance of the new tissue(s)

“Wandering” bacteria causing disease Pneumococci from pharynx to lung Polio virus from gut to CNS Colon bacilli from gut to urogenital tract (bladder infections) to peritoneal cavity (peritonitis) Oral flora from oral cavity to root canal to periodontal pocket

Properties Determining Pathogenicity TRANSMISSIBILITY - ease of transmission

Transmissibility Depends on 3 Factors 1. Number of bacteria liberated per unit time 2. Length of time host actually liberates bacteria Some bacteria have periods of liberation Ex. Whooping cough and TB

Transmissibility Depends on 3 Factors 3. Ability to survive outside the host T. pallidum survives only a few minutes - thus, direct contact is necessary B. anthracis may survive in infected soil for decades

Transmissibility Depends on 3 Factors Ability to survive outside host (continued) Staphylococci and beta strep - withstand drying for days, weeks, or months Anaerobes - depends on how strict they are

Transmissibility Depends on 3 Factors Ability to survive outside host (continued) Hepatitis B - up to 1 week dried on surfaces Herpes - over 9 days dried on surfaces AIDS - ~ only a few hours if dried ~ a week if kept moist

Transmissibility There are 6 modes of transmission 1.  INGESTION of food or drink contaminated with fecal material Ex. Typhoid, paratyphoid, dysentery, cholera, hepatitis types A and E

Transmissibility Modes of transmission (continued) 2.  INHALATION of airborne droplets Ex. Diphtheria, strep. throat, TB, epidemic meningitis, whooping cough, legionellosis, many viral diseases

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Transmissibility Modes of transmission (continued) 3.  DIRECT CONTACT with infected person’s bodily fluids or secretions Ex. Syphilis, gonorrhea, other venereal diseases, hepatitis B, C, & D; AIDS and possibly caries and periodontal disease(s) Ex. In dentistry needle injection of hepatitis B,C,& D; AIDS

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Transmissibility Modes of transmission (continued) 4.  INJECTION into the blood or tissues by an insect bite Ex. Plague, rocky mountain spotted fever, malaria, rabies

Transmissibility Modes of transmission (continued) 5.  INTRODUCTION OF FOREIGN MATERIAL INTO A WOUND Ex. Many localized infections-soil clostridia, human bite infections, tetanus In dentistry endodontic/root canal post surgical abscess needle injection of hepatitis B,C,& D; AIDS

Transmissibility Modes of transmission (continued) 6.  PLACENTAL PASSAGE - mother to child Ex. Syphilis, toxoplasmosis, rubella (german measles), AIDS

Infectivity  (ability to establish itself in a host-to be retained at a particular site) Infectivity depends on 3 things 1. Proper Eh 2. Ability to attach to tissues 3. Availability of the right nutrients

"1." 1. Proper Eh Eh is a measure of the oxidation-reduction potential A positive Eh is indicative of an aerobic environment A negative Eh is indicative of an anaerobic environment Anaerobes and aerobes need right Eh

"2." 2. Ability to attach to tissues In the mouth - either the hard or soft tissues Usually done via pili or fimbriae or glucan synthesis, sometimes via a capsule

Relationship between epithelial cell adherence in vitro and bacterial infectivity in vivo Bacteria Variant Adhere Infectivity A. viscosus Fimbriate Good High Nonfimbriate Poor Low S. mutans Dextran + Good High Dextran - Poor Low

"Infectivity depends on" Infectivity depends on 3. Availability of Right Nutrients HEME & VITAMIN K - needed by many anaerobes Heme is often obtained from red blood cells via lysis Vitamin K is produced by other bacteria

"3." 3. Availability of Right Nutrients (continued) IRON - needed by all bacteria Must compete with the animal’s Iron binding proteins: Transferrin-iron binding glycoprotein in serum Lactoferrin-transferrin produce by white blood cells and found in mucosal secretions

Infectivity  3. Availability of Right Nutrients IRON continued Bacteria may produce Siderophores Chemicals released extracellularly that convert iron compounds into a form bacteria can use

Virulence (relative ability to cause disease) Depends on: Invasiveness Toxigenicity Toxicity Other factors

Virulence  Invasiveness INVASIVENESS - the relative ability to resist the host’s defenses

Virulence Invasiveness Host defenses may be specific and nonspecific SPECIFIC DEFENSES are the Immune related activities

Virulence Invasiveness NONSPECIFIC DEFENSES include Skin Physical barrier Chemical barrier - fatty acids & lysozyme

Virulence Invasiveness Nonspecific Defenses Normal skin flora Organisms that resist the skin’s defenses and don’t cause infection They fill the niche and therefore prevent other organisms from becoming established

Virulence Invasiveness Nonspecific Defenses Mucus in the mouth Bacteria stick to the mucous and are swallowed Saliva Continually washes the mouth Contains lysozyme and IgA

Virulence Invasiveness Nonspecific Defenses Acid in the stomach Kills most ingested bacteria Tears Mechanical flushing action Contain lysozyme

Virulence Invasiveness Bacteria resist these host defenses in many ways

Virulence Invasiveness Methods of Bacterial Resistance Capsules Allow the bacterium to resist phagocytosis by interfering with: Attraction of the phagocyte Engulfment (phagocytosis) Recognition of the cell as foreign

Virulence Invasiveness Methods of Bacterial Resistance Some strep form a hyaluronic acid capsule which prevents the body from recognizing them as foreign Nevertheless, some encapsulated strains of  pathogenic species are avirulent so more than a capsule is needed to cause an infection

Virulence Invasiveness Methods of Bacterial Resistance Slimes Capsular material when free in solution may inhibit phagocytosis In mixed infections the presence of a slime of one bacterial species may protect neighboring unrelated bacteria from phagocytosis

Virulence Invasiveness Methods of Bacterial Resistance Survival In The Phagocyte Staphylococcus aureus does survive Staphylococcus epidermidis does not survive Neisseria gonorrhoeae does survive

Virulence Invasiveness Methods of Bacterial Resistance Absorption Of Host Materials To Cell Wall S. aureus absorbs gamma globulin to the cell wall via its protein A reacting with the Fc portion of the globulin Prevents body from recognizing cell as foreign

Virulence Invasiveness Methods of Bacterial Resistance Hyaluronidase Collagenase Fibrinolysin Coagulase Mucinase IgA1 Protease Other proteases Nucleases Lipases

Virulence Invasiveness Methods of Bacterial Resistance HYALURONIDASE-breaks down hyaluronic acid of the connective tissue This may contribute to the spread of the bacteria through the tissues

Virulence Invasiveness Methods of Bacterial Resistance COLLAGENASE Breaks down collagen-the main constituent of connective tissue

Virulence Invasiveness Methods of Bacterial Resistance FIBRINOLYSIN Dissolves blood clots (fibrin) and may aid in spreading the organisms

Virulence Invasiveness Methods of Bacterial Resistance COAGULASE Produced by staphylococci Converts soluble fibrinogen to insoluble fibrin

Virulence Invasiveness Methods of Bacterial Resistance COAGULASE 1. Can form a fibrin wall around the bacteria-preventing dispersal but allowing the buildup of higher levels of toxins

Virulence Invasiveness Methods of Bacterial Resistance COAGULASE 2. Cause a layer of fibrin to be deposited on the cell surface forming a sort of “capsule” that prevents the host from recognizing the organism as foreign

Virulence Invasiveness Methods of Bacterial Resistance MUCINASE Produced by Vibrio cholera Destroys the mucous layer that lines the bowel and exposes the underlying cells to the toxic action of the vibrio

Virulence Invasiveness Methods of Bacterial Resistance IgA1 PROTEASE Produced by several bacteria involved in periodontal disease IgA normally neutralizes toxins, enzymes, and viruses inhibits the adherence of bacteria to mucosal and hard surfaces

"Other Proteases" Other Proteases HEMOGLOBINASE GELATINASE

"NUCLEASES" NUCLEASES Break down DNA and RNA liberated by lysed white cells Nucleic acids are normally viscous and serve to keep the organisms confined to the area, allowing other cells to migrate to the area and hopefully kill the invading bacterial cell

"LIPASES Possibly active in skin..." LIPASES Possibly active in skin infections

Virulence Toxigenicity Virulence also depends on Toxigenicity Microbial products which damage or kill the normal host or host cells are called toxins There are 2 types of bacterial toxins: Extracellular (exotoxins) Cellular (some called endotoxins)

Virulence Toxigenicity Exotoxins Generally heat-labile proteins Generally produced by Gram-positive organisms Generally found in solution when grown in fluid medium-therefore they are considered extracellular or exotoxins

Virulence Toxigenicity Exotoxins Most exotoxins have 2 subunits: 1. nontoxic unit - binds to specific receptors 2. toxic unit

Virulence Toxigenicity Exotoxins Many toxin genes are encoded by phage, plasmids, or transposons Transposons-segments of DNA that carry genes from one chromosomal location to another: from chromosome to plasmid plasmid to plasmid plasmid to chromosome

Virulence Toxigenicity Exotoxins Example In Corynebacterium diphtheria, only cells which are lysogenic   for a particular prophage can produce exotoxin

Virulence Toxigenicity Exotoxins Mode of Action of Exotoxins Enzymes Neurotoxins Enzyme poisons Leukocidins

Virulence Toxigenicity Exotoxins ENZYMES Damage the host by digesting essential cell components Alpha toxin of C. perfringens is a lecithinase lyses erythrocytes - hemolysin lyses leukocytes - leukocidin

Virulence Toxigenicity Exotoxins NEUROTOXINS Botulinum toxin and tetanus toxin 1 billionth of a gram of botulinum toxin (botulin) contains enough toxin to kill 20 mice Botulin causes respiratory failure, paralysis and death in 4 hrs

Virulence Toxigenicity Exotoxins ENZYME POISONS Yersinia pestis strongly inhibits the respiration of mitochondria

Virulence Toxigenicity Exotoxins LEUKOCIDINS Cause death of white cells Staphylococcus aureus alpha-hemolysin, delta hemolysin, Pantin-Valentine leukocidin Actinobacillus actinomycetemcomitans

Virulence Toxigenicity Exotoxins Note the extensive table in the handout showing exotoxins produced by various toxigenic bacteria

Virulence Toxigenicity Cellular ENDOTOXINS Heat-stabile lipopolysaccharide (LPS)-protein complexes Produced by Gram-negative bacteria Released upon the death of the cell Small quantities released by living cells

Virulence Toxigenicity Cellular Endotoxins (con’t) Activate C’ pathway at C’3 Irreversible shock - cardiovascular collapse Platelet agglutination Bone resorption

Virulence Toxigenicity Cellular Endotoxins (con’t) Pyrogenic via lipid Toxic via lipid Antigenic via protein & polysaccharide Mitogenic - stimulates multiplication of lymphocytes Hemorrhagic

Virulence Toxigenicity Cellular Endotoxins (con’t) Endotoxin produces inflammation via increased capillary permeability and cellular injury The cellular injury of PMN leukocytes causes the release of an endogenous pyrogen (endotoxin isn’t directly pyrogenic)

Virulence Toxigenicity Cellular LIMULUS TEST - laboratory test for endotoxin Uses a lysate of amebocytes of the horseshoe crab (genus Limulus) The lysate gels or precipitates in the presence of endotoxin

Measuring Endotoxin Originally, the only way to measure endotoxin was by injecting rabbits and monitoring them for an increase in temperature (pyrogenicity)

Horseshoe Crab

Endotoxin test Limulus Test = laboratory test for endotoxin A lysate of the amebocytes of the horseshoe crab (genus Limulus) gels or precipitates in the presence of endotoxin

Virulence Toxigenicity Cellular PEPTIDOGLYCAN A cell wall component of Gram-positive bacteria

Virulence Toxigenicity Cellular Peptidoglycan Effects Complement activation Pyrogenic Stimulation of reticuloendothelial system Immunopotentitation Bone resorption Stimulate macrophages to produce prostaglandin and collagenase

Virulence Toxigenicity Cellular LIPOTEICHOIC ACID Only in Gram-positive cell walls Binds to cell membranes - mainly lymphocytes and macrophages Causes cell activation - immuno-potentiation

Virulence Toxigenicity Cellular LIPOTEICHOIC ACID con’t Induce bone resorption Activate complement

Virulence Toxicity of Metabolic Waste Products Lactic acid -demineralize enamel NH4 -histotoxic H2S -histotoxic Fatty Acids -histotoxic, leukotoxic, inhibit chemotaxis and phagocytosis

Virulence Unknown Factors (Includes) SYNERGISM - activity produced is greater than the sum of the two activities 1 + 1 = 3

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"Congratulations!" Congratulations! You have completed the first 1/3 of the course Good Luck on the exam