Pathogenesis of Bacterial Infection

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<p>PATHOGENESIS OF BACTERIAL INFECTIONGLOSSARY Jawetz Medical Microbiology, 26th Ed., pp. 149-150 Characteristics of Pathogenic Bacteria:1. Transmissibility2. Adherence to host cells3. Persistence4. Invasion of host cells and tissues5. Toxigenicity6. Ability to evade or survive the hosts immune system Identifying Bacteria that Cause Disease1. KOCHS POSTULATES (1884)2. MOLECULAR KOCHS POSTULATES3. MOLECULAR GUIDELINES FOR ESTABLISHING MICROBIAL DISEASE CAUSATIONVIRULENCE Quantitative measure of pathogenicity Measured by the number of organisms required to cause diseaseLD50 (50% lethal dose)- # of organisms needed to kill half of the hostsID50 (50% infectious dose)- # of organisms needed to cause infection in half ofthe hosts Bacteria cause disease by:1. Toxin Production2. Invasion And Inflammation3. Immunopathogenesis</p> <p> Types of Bacterial Infection:EPIDEMIC occurs much more frequently than usualPANDEMIC worldwide distributionENDEMIC constantly present at a low level in a specific populationINAPPARENT/SUBCLINICAL detected only by demonstrating a rise in antibody titer or by isolating the organismLATENT STATE reactivation of the growth of the organism and recurrence of symptoms may occurCHRONIC CARRIER STATE organisms continue to grow with or without producing symptoms in the host</p> <p>STAGES OF BACTERIAL PATHOGENESIS:1. TRANSMISSION from an external source into the portal of entry2. EVASION of primary host defenses (skin, stomach acid)3. ADHERENCE to mucous membranes usually by bacterial pili4. COLONIZATION by growth of the bacteria at the site of adherence5. DISEASE SYMPTOMS caused by toxin production or invasion accompanied by inflammation6. HOST RESPONSES (nonspecific, specific)7. PROGRESSION or RESOLUTION of the disease</p> <p>GENOMICS &amp; BACTERIAL PATHOGENICITYMechanisms used by bacteria to transmit virulence genes from one to another:1. Transformation- DNA from one organism is released into theenvironment and is taken up by a different organism that is capable of recognizing and binding DNA2. Mobile genetic elements- plasmids, transposons, bacteriophages</p> <p>VIRULENCE FACTORS ENCODED BY GENES ON MOBILE GENETIC ELEMENTS(Table 9-2, p153)PATHOGENICITY ISLANDS (PAIs)Large group of genes that are associated with pathogenicity located on bacterialchromosomes; 10-200 kbProperties:1. &gt; 1 virulence genes2. present in the genome of pathogenic members of a species, absent in nonpathogenic members 3. large4. different guanine + cytosine content (G+C) than the rest of the bacterial genome5. commonly associated with tRNA genes6. often found with parts of the genome associated with mobile genetic elements7. often have genetic instability8. often represent mosaic structures with components acquired at different times</p> <p>DETERMINANTS OF BACTERIAL PATHOGENESISI. TRANSMISSIONII. ADHERENCE TO CELL SURFACESIII. INVASION, INFLAMMATION &amp; INTRACELLULAR SURVIVALIV. TOXIN PRODUCTIONV. IMMUNOPATHOGENESIS</p> <p> TRANSMISSIONAn understanding of the mode of transmission of bacteria and other infectious agents is important because interrupting the chain of transmission is an excellent way to prevent infectious diseases.</p> <p>IMPORTANT MODES OF TRANSMISSIONMode of TransmissionClinical Example</p> <p>I. HUMAN TO HUMAN</p> <p> A. Direct ContactGonorrheaIntimate contact (sexual or passage through birth canal)</p> <p> B. No direct contactDysenteryFecal-oral (excreted in human feces, then ingested in food or water)</p> <p> C. TransplacentalCongenital syphilisBacteria cross the placenta and infect the fetus</p> <p> D. Blood-borneSyphilisTransfused blood or IV drug use can transmit bacteria and viruses</p> <p>II. NONHUMAN TO HUMAN</p> <p>A. Soil SourceTetanusSpores in soil enter wound in skin</p> <p>B. Water SourceLegionnaires DiseaseBacteria in water aerosol are inhaled into lungs</p> <p>C. Animal Source 1. Directly 2. Via insect vector 3. Via animal excretaCat-scratch FeverLyme Disease</p> <p>HUS by E. coli 0-157Bacteria enter in cat scratchBacteria enter in tick bite</p> <p>Bacteria in cattle feces are ingested in undercooked hamburger</p> <p>D. Fomite SourceStaphylococcal skin infectionBacteria on an object (towel) are transferred onto the skin</p> <p>VERTICAL TRANSMISSION from mother to offspringWithin birth canal/ at the time of birthStreptococcus agalactiae (Group B streptococci)Neonatal sepsis and meningitis</p> <p>Escherichia coliNeonatal sepsis and meningitis</p> <p>Chlamydia trachomatisConjunctivitis and pneumonia</p> <p>Neisseria gonorrhoeaeConjunctivitis</p> <p>Herpes simplex type-2Skin, CNS, disseminated infection (sepsis)</p> <p>Hepatitis B virusHepatitis B</p> <p>Human immune-deficiency virusAsymptomatic infection</p> <p>Candida albicansThrush</p> <p>Breast milkStaphylococcus aureusOral or skin infections</p> <p>CytomegalovirusAsymptomatic infection</p> <p>Human T-cell leukemia virusAsymptomatic infection</p> <p>TransplacentalTreponema pallidumCongenital syphilis</p> <p>Listeria monocytogenesNeonatal sepsis and meningitis</p> <p>CytomegalovirusCongenital abnormalities</p> <p>ParvovirusHydrops fetalis</p> <p>Toxoplasma gondiiToxoplasmosis</p> <p>IMPORTANT PORTALS OF ENTRY1. respiratory tract(upper and lower airways)2. GIT (primarily mouth)3. genital tract4. urinary tractPortal of EntryPathogenDisease</p> <p>Respiratory TractStreptococcus pneumoniaePneumonia</p> <p>Neisseria meningitidesMeningitis</p> <p>Haemophilus influenzaMeningitis</p> <p>Mycobacterium tuberculosisTuberculosis</p> <p>Influenza virusInfluenza</p> <p>RhinovirusCommon cold</p> <p>Epstein-Barr virusInfectious mononucleosis</p> <p>Coccidiodes immitisCoccidiodomycosis</p> <p>Histoplasma capsulatumHistoplasmosis</p> <p>GITShigella dysenteriaeDysentery</p> <p>Salmonella typhiTyphoid fever</p> <p>Vibrio choleraCholera</p> <p>Hepatitis A virusInfectious hepatitis</p> <p>PoliovirusPoliomyelitis</p> <p>Trichinella spiralisTrichinosis</p> <p>SkinClostridium tetaniTetanus</p> <p>Rickettsia rickettsiRocky Mountain Spotted Fever</p> <p>Rabies virusRabies</p> <p>Trichophyton rubrumTinea pedis (athletes foot)</p> <p>Plasmodium vivaxMalaria</p> <p>Genital TractNeisseria gonorrhoeaeGonorrhea </p> <p>Treponema pallidumSyphilis</p> <p>Chlamydia trachomatisUrethritis</p> <p>Human papilloma virusGenital warts</p> <p>Candida albicansVaginitis</p> <p>TRANSMISSION OF IMPORTANT WATERBORNE DISEASESPortal of EntryPathogenDisease</p> <p>Respiratory Tract</p> <p>Inhalation of water aerosolLegionella pneumophilaPneumonia (Legionnaires disease)</p> <p>Skin</p> <p>Penetration through skinPseudomonas aeruginosaHot-tub folliculitis</p> <p>Schistosoma mansoniSchistosomiasis </p> <p>Nose</p> <p>Penetration through cribriform plateNaegleria fowleriMeningoencephalitis</p> <p>Gastrointestinal Tract</p> <p>1. Ingestion of drinking waterSalmonella speciesDiarrhea</p> <p>Shigella speciesDiarrhea</p> <p>Campylobacter jejuniDiarrhea</p> <p>Norovirus (Norwalk-like viruses)Diarrhea</p> <p>Giardia lamblliaDiarrhea</p> <p>Cryptosporidium parvumDiarrhea</p> <p>2. Ingestion of water while swimmingLeptospira interrogansLeptospirosis</p> <p>DIARRHEAL DISEASES TRANSMITTED BY FOODBacteriumTypical FoodMain ReservoirDisease</p> <p>Diarrheal Diseases</p> <p>Gram-positive cocci Staphylococcus aureusCustard-filled pastries, potato, egg, tuna fish saladHumansFood poisoning, esp. vomiting</p> <p>Gram-positive rods Bacillus cereus Clostridium perfringens Listeria monocytogenesReheated riceCooked meat, stew and gravyUnpasteurized milk productsSoilSoil, animals or humansSoil, animals or plantsDiarrheaDiarrhea</p> <p>Diarrhea</p> <p>Gram-negative rods Eschericia coli E. coli O157:H7 strain Salmonella enteritidis Salmonella typhi Shigella species Vibrio cholera Vibrio parahaemolyticus Campylobacter jejuni Yersinia enterocoliticaVarious foods and waterUndercooked meat</p> <p>Poultry, meats and eggs</p> <p>Various foodsVarious foods and waterVarious foods and waterSeafoodVarious foodsVarious foodsHumansCattle</p> <p>Domestic animals (esp. poulty)HumansHumansHumansWarm salt waterDomestic animals Domestic animals DiarrheaHemorrhagic colitis</p> <p>Diarrhea</p> <p>Typhoid FeverDiarrheaDiarrhea (dysentery)DiarrheaDiarrheaDiarrhea</p> <p>Nondiarrheal Diseases</p> <p>Gram-positive rods Clostridium botulinum Listeria monocytogenesImproperly cannedvegetables and smoked fishUnpasteurized milk productsSoil</p> <p>CowsBotulism</p> <p>Sepsis in neonate or mother</p> <p>Gram-negative rodsVibrio vulnificusBrucella speciesFrancisella tularensis SeafoodMeat and milkMeatWarm salt waterDomestic animalsRabbitsSepsisBrucellosisTularemia</p> <p>Mycobacteria Mycobacterium bovisMilkCowsIntestinal tuberculosis</p> <p>BACTERIAL DISEASES TRANSMITTED BY INSECTSBacteriumInsect ReservoirDisease</p> <p>Gram-negative rods Yersinia pestis Francisella tularensisRat fleas</p> <p>Ticks (Dermacentor)Rodents (rats, prairie dogs)</p> <p>Many animals (rabbits)PlagueTularemia</p> <p>Spirochetes Borrelia burgdorferi Borrelia recurrentisTicks (Ixodes)HumansMiceHumansLyme diseaseRelapsing fever</p> <p>Rickettsias Rickettsia rickettsia Rickettsia prowazekii Ehrlichia chaffeensisTicks (Dermacentor)LiceTicks (Dermacentor, Ixodes)Dogs, rodents, ticks </p> <p> ADHERENCE TO CELL SURFACESPILI (Neisseria gonorrhoeae, Escherichia coli)CAPSULESGLYCOCALYCES (Staphylococcus epidermidis, viridans streptococci)Various molecules that mediate adherence to cell surfaces are called ADHESINS</p> <p> INVASION, INFLAMMATION &amp; INTRACELLULAR SURVIVALENZYMES1. COLLAGENASE degrade collagen 2. HYALURONIDASE degrade hyaluronic acid3. COAGULASE accelerates the formation of fibrin clot from fibrinogen; clot protects the bacteria from phagocytosis by walling off the infected area and coating the microorganism4. IMMUNOGLOBULIN A (IgA) PROTEASE degrades IgA5. LEUKOCIDINS destroy neutrophilic leukocytes and macrophages</p> <p>VIRULENCE FACTORS1. CAPSULE Streptococcus pneumoniae, Neisseria meningitidis</p> <p>6. CELL WALL PROTEINS OF GRAM (+) COCCI M protein (group A streptococci Streptococcus pyogenes, Protein A of Staphylococcus aureus)INTRACELLULAR SURVIVALMycobacterium, Legionella, Brucella, Listeria, Histoplasma1. inhibition of the fusion of phagosome with the lysosome (avoid degradative enzymes in the lysosome)2. inhibition of acidification of the phagosome (reduces activity of lysosomal degradative enzymes )3. escape from phagosome into the cytoplasm (no degradative enzymes )</p> <p>Bacteria cause disease by: INFLAMMATION and TOXIN PRODUCTION</p> <p> TOXIN PRODUCTIONMAIN FEATURES OF EXOTOXINS AND ENDOTOXINSPROPERTYEXOTOXINENDOTOXIN</p> <p>SourceCertain species of G(+) &amp; Gram (-) bacteriaCell wall of G(-) bacteria</p> <p>Secreted from cellYesNo</p> <p>ChemistryPolypeptideLipopolysaccharide</p> <p>Location of genesPlasmid or bacteriophageBacterial chromosome</p> <p>ToxicityHigh Low</p> <p>Clinical effectsVariousFever, shock</p> <p>Mode of actionVariousIncludes TNF, IL-1</p> <p>AntigenicityInduces high-titer antibodies (antitoxins)Poorly antigenic</p> <p>VaccinesToxoids used as vaccinesNo toxoids formed and no vaccines available</p> <p>Heat stabilityDestroyed rapidly at 60oC (except staphylococcal enterotoxin)Stable at 100oC for 1 hour</p> <p>Typical diseasesTetanus, botulism, diphtheriaMeningococcemia, sepsis</p> <p>EFFECTS OF ENDOTOXINS</p> <p>CLINICAL FINDINGSMEDIATOR/MECHANISM</p> <p>FEVERIL-1, IL-6</p> <p>HYPOTENSION (SHOCK)TNF, NITRIC OXIDE, BRADYKININ</p> <p>INFLAMMATIONC5a produced by the alternative pathway of complement attracts neutrophils </p> <p>COAGULATION (DIC)Activation of tissue factor</p> <p>EXOTOXINS have A-B subunit A (active)- possesses the toxic activityB (binding)- responsible for binding the exotoxin to specific receptors on the membrane of the human cell) A-subunit: act by ADP-ribosylation (A-subunit is an enzyme that catalyzes the addition of adenosine diphosphate ribose- ADP-ribose- to the target protein in the human cell INACTIVATES or HYPERACTIVATE THE CELL SYMPTOMS EXOTOXINS are released from bacterial by SECRETION SYSTEMS INJECTOSOME/TYPE III SECRETION SYSTEM molecular syringe (needle-like projection) &amp; transport pumps in the bacterial cell membrane</p> <p>IMPORTANT MECHANISMS OF ACTION OF BACTERIAL EXOTOXINS</p> <p>IMPORTANT BACTERIAL EXOTOXINSMECHANISM OF ACTIONEXOTOXIN</p> <p>ADP- ribosylationDiphtheria toxin, cholera toxin, Escherichia coli heat-labile toxin, pertussis toxin</p> <p>SuperantigenTSST, staphylococcal enterotoxin, erythrogenic toxin</p> <p>ProteaseTetanus toxin, botulinum toxin, lethal factor of anthrax toxin, scalded skin toxin</p> <p>LecithinaseClostridium perfringens alpha toxin</p> <p>BACTERIUMMECHANISM OF ACTION</p> <p>Corynebacterium diphtheriaInactivates EF-2 by ADP-ribosylation (inhibits protein synthesis)</p> <p>Clostridium tetaniBlocks the release of the inhibitory NT GLYCINE by proteolytic cleavage of releasing proteins</p> <p>Clostridium botulinumBlocks release of ACETYLCHOLINE by proteolytic cleavage of releasing proteins</p> <p>Clostridium difficileExotoxins A and B inactivate GTPases by glycosylation</p> <p>Clostridium perfringensAlpha toxin is a lecithinase; enterotoxin is a superantigen</p> <p>Bacillus anthracisEdema factor is an adenylate cyclase; lethal factor is a protease that cleaves MAP kinase (required for cell division)</p>