PowerPoint Presentation - Microbes and Human Welfare

How Microbes Cause Diseases: Examples in Various SystemsChapter 151ObjectivesIdentify the principle port of entryExplain how microbes adhere and enter the host cellExplain how microbes evade the host immune systemHow do microbes damage host cells?How do microbes exit the host?Pathogenicity: The ability to cause a disease by overcoming the defenses of the hostVirulence: virulent vs avirulentThe degree of pathogenicityWhat factors contribute to the occurrence of a disease?Pathogens produce virulence factors that assist a pathogen to enter a host, evade host defenses, damage to host cells, and exit the hostWhy do we study bacterial pathogenesis? Microbial Mechanisms of Pathogenicity

Mechanisms of PathogenicityFig. 15.91234

1. Portals of EntryMucous membranes lining Respiratory, GI, genitourinary tracts and eyesRespiratory tract: Easiest & most common route; e.g. common cold, TB, influenza & measlesGI tract accessed via food and water (most m/os are destroyed by stomach HCl, enzymes & bile); e.g. typhoid fever, hepatitis & choleraSexually transmitted m/os may penetrate an unbroken mucous membrane of genitourinary tractSkinLargest organ of the body & an important defenseM/os access body via hair follicles & sweat gland ductsParenteral routeDeposit m/os beneath the skin & mucous membranes via injections, bites, cuts, surgery, etc.; e.g. HIV & hepatitis

Factors that contribute to disease:Preferred portal of entrySalmonella typhi: GI tractStreptococcus pneumonia:respiratory tractYersinia pestis: parenteral routeNumbers of invading m/osVirulence often expressed as ID50Infectious dose for 50% of populationPotency often expressed as LD50Lethal dose for 50% of the populationBotulinum toxin (0.03 ng/kg) 1

Portal of Entry (Bacillus anthracis)ID50EndosporesSkin10-50Inhalation10,000-20,000Ingestion250,000-1,000,000Numbers of M/Os & Preferred Portal of EntryCutaneous anthrax is significantly easier to acquire than either inhalation or ingestion formsToxinPort of EntryID50 (ng/kg)BotulinumGIT0.03Shiga toxinGIT250Staphylococcal enterotoxinGIT1350

2A. How Bacteria Penetrate (Invade) Host Defenses - AdherenceMicrobes must attach to host cells at portal of entry_____________or ligands (glycoproteins or lipoproteins) on microbes bind to receptors on host cells _______________& cell wall components Glycocalyx: Streptococcus mutans: surface of teethFimbriae: Enteropathogenic Escherichia coliFimbriae: Neisseria gonorrhoeae: in genitourinary tractTapered end as a hook: Treponema pallidum

Penetration into the Host Cell CytoskeletonFigure 15.2

Adhesins/Invasin: Attach to host cells______________: Rearrange nearby host cell cytoskeleton and induce ______________M/os sink into the ruffles and are engulfed by the host cellM/os can use cytoskeleton to move through and between cells

2B. How Pathogens Evade Host DefensesVirulence of some bacteria is aided by: ____________: impair phagocytosisStreptococcus pneumoniae____________: resist digestion by phagocytesMycobacterium tuberculosis____________: Coagulate the fibrinogen in bloodStaphylococcus aureus____________: Digest fibrin clotsStreptococcus pyogenes, Staphylococcus aureusHyaluronidase: Hydrolyses hyaluronic acid that holds together some cells in body (i.e. connective tissue)Streptococcus spp, Clostridium spp____________: Hydrolyzes collagenClostridium sppIgA proteases: Destroy IgA antibodiesNeisseria gonorrhoeae

Antigenic VariationM/os alter _______________to evade hosts immune systemBy the time the body mounts an immune response, the m/os has altered its ____________and is unaffected by antibodiesInfluenzavirus (influenza, H & N)Neisseria gonorrhoeae (gonorrhea, Opa)Trypanosoma brucei gambiense (trypanosomiasis, surface proteins)

3. Damage to Host Cells

Siderophores:Take iron from host cells/proteins (transferrin)Direct damage:Some pathogens grow inside host cellsVirusesSalmonellaN. gonorrhoeae

13Microbial ToxinsPrimary factors contributing to pathogenic properties of microbesToxins Transported by blood or lymphMay produce fever, cardiovascular disturbances, diarrhea or shock; Inhibit protein synthesis, destroy blood cells or disrupt nervous systemTwo major types of toxins________________(secreted by live bacteria)________________(produced during decomposition of bacteria)ExotoxinSource:Mostly Gram (+)Relation to microbe:By-products of growing cellChemistry:ProteinFever?NoNeutralized by antitoxin?YesLD50:SmallFigure 15.5

Proteins produced inside pathogenic bacteria, most commonly __________________, as part of their growth & metabolism; secreted in surrounding medium during log phaseExotoxinFigure 15.5Three major typesA-B toxinsActive/Binding components(Diptheria toxin, botulinum toxin, cholera toxin)Membrane disrupting toxins (lyse cells)Hemolysins production (Streptococcus & Staphylococcus spp)SuperantigensCause an intense immune response due to release of cytokines from host cells (T cells)Fever, nausea, vomiting, diarrhea, shock & deathE.g. enterotoxin ofS. aureus

Source:Gram ()Relation to microbe:Present in LPS of outer membraneChemistry:LipidFever?YesNeutralized by antitoxin?NoLD50:Relatively largeFigure 15.4bEndotoxinsPart of cell wall of _______________ bacteriaSymptoms similar for different bacteriaReleased when bacteria dies or during multiplicationActivate blood clotting factors that may obstruct capillaries

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Fig. 15.6

Plasmids, Lysogeny & PathogenicityPlasmids: Small, circular DNA molecules not connected to bacterial chromosomeEncode gene for resistance to antibiotics, exotoxins (tetanus neurotoxin, staphylococcal enterotoxin), and other virulence factors Lysogeny: is bacteriophages that can incorporate their DNA into bacterial chromosome and becoming a prophageProphage: genes can contribute to bacterial pathogenicity such as diphtheria toxin, staphylococcal enterotoxin, botulinum neurotoxin and the capsule produced by S. pneumoniaeMicroevolution: A way to increase the number of pathogenic bacteria?

4. Portals of ExitM/os can exit host via secretions, excretions, discharges, or tissue that has been shedM/o mostly use the same portal for entry and exitEnd goal Spread through the populationRespiratory tract (most common route)Coughing and sneezingGastrointestinal tractFeces and salivaGenitourinary tractUrine and vaginal secretionsSkin (how?)BloodBiting arthropods and contaminated needles or syringes