Chapter 15 Microbial Mechanisms of Pathogenicity Pathogenicity the ability to cause disease by overcoming the defenses of a host Virulence the degree of extent of pathogenicity I How Microorganisms Enter a Host a Portals of Entry i Mucous Membranes 1 Many bacteria and viruses gain access to the body by penetrating mucous membranes lining the respiratory tract gastrointestinal tract genitourinary tract and conjunctiva 2 Most enter through the gastrointestinal and respiratory tracts ii Skin iii The Parenteral Route 1 When they are deposited directly into the tissues beneath the skin or into mucous membranes when these barriers are penetrated or injured b The Preferred Portal of Entry i Pathogens do not always cause a disease ii Occurs most likely when entry into the body is by the preferred portal of entry iii Ie Salmonella typhi causes typhoid fever when swallowed but only produces a slight inflammation is rubbed on the skin c Numbers of Invading Microbes i The likelihood of disease increases as the number of pathogens increase ii iii LD50 lethal dose for 50 of a sample population ID50 the infectious dose for 50 of a sample population d Adherence portal of entry i The most common way pathogens attach themselves to host tissues at their ii Adhesins ligands the attachment between pathogen and host is accomplished by these surface molecules iii Receptors complementary to the adhesins ligands 1 Majority of adhesins are glycoproteins or lipoproteins 2 Majority of receptors are sugars such as mannose iv Biofilms the ability to come together in masses cling to surfaces and take in and share available nutrients the communities which constitute masses of microbes and their extracellular products that can attach to living and nonliving surfaces 1 The first microbes to attach are usually bacteria once they adhere to the surface they multiply and secrete a glycocalyx that further attaches the bacteria to each other and to the surface II How Bacterial Pathogens Penetrate Host Defenses 2 Biofilms resist disinfectants and antibiotics a Capsules i Capsules increase the virulence of species ii Capsules resist the host s defenses by impairing phagocytosis iii The chemical nature of the capsule appears to prevent the phagocytic cell from adhering to the bacterium b Cell Wall Components virulence i The cell walls of certain bacteria contain chemical substances that contribute to ii M protein a heat resistant and acid resistant protein found on both the cell surface and fimbriae the M protein mediates attachment of the bacterium to epithelial cells of the host and helps the bacterium resist phagocytosis by white blood cells the protein thereby increases the virulence of the microorganism iii Opa used by microorganisms along with fimbriae to attach to host cells iv Waxy lipid also increases virulence by resisting digestion by phagocytes and can even multiply inside phagocytes c Enzymes i Coagulases bacterial enzymes that coagulate clot the fibrinogen in blood ii Fibrinogen a plasma protein produced by the liver is converted by coagulases into fibrin the threads that form a blood clot 1 the fibrin clot may protect the bacterium from phagocytosis and isolate it from other defenses of the host iii Kinsases bacterial enzymes that break down fibrin and thus digest clots formed by the body to isolate the infection iv Fibrinolysis a well known kinase v Hyaluronidase an enzyme secreted by certain bacteria that hydrolyzes hyaluronic acid a type of polysaccharide that holds together certain cells of the body particularly cells in connective tissue vi Collagenase is produced by several species of Clostridium and facilitates the spread of gas gangrene breaks down the protein collagen which forms the connective tissue of muscles and other body organs and tissues IgA proteases have the ability to destroy IgA antibodies vii d Antigenic Variation i Changes in surface antigens that occur in a microbial population e Penetration into the Host Cell Cytoskeleton Invasins rearrange nearby actin filaments of the cytoskeleton i ii Membrane ruffling invasins of the microbe cause the appearance of the host cell plasma membrane to resemble the splash of a drop of liquid hitting a sold surface this is the result of disruption in the cytoskeleton of the host cell the microbe sinks into the ruffle and is engulfed by the host cell III How Bacterial Pathogens Damage Host Cells a Using the Host s Nutrients Siderophores i Siderophores some pathogens secrete this protein in order to obtain free iron b Direct Damage i Once pathogens attach to host cells they can cause direct damage as the pathogens use the host cell for nutrients and produce waste products ii Many viruses and some intracellular bacteria and protozoa that grow in host cells are release when the host cell ruptures following their release pathogens that rupture cells can spread to other tissues in even greater numbers c The Production of Toxins i Toxins poisonous substances that are produced by certain microorganism ii They are often the primary factor contributing to the pathogenic properties of these microbes fatal effects iii Toxigenicity the capacity of microorganisms to produce toxins iv Toxins transported by the blood or lymph can cause serious and sometimes v Toxins can also inhibit protein synthesis destroy blood cells and blood vessels and disrupt the nervous system by causing spasms vi Toxemia refers to the presence of toxins in the blood vii Toxins are of two general types based on their position relative to the microbial cell exotoxins and endotoxins 1 Exotoxins a Are produced inside some bacteria as part of their own growth and metabolism and are secreted by the bacterium into the surrounding medium or released by lysis Small amounts are quite harmful or even lethal b Proteins c d Can be gram negative or gram positive e The genes for most are carried on bacterial plasmids or phages f Soluble in body fluids they can easily diffuse into the blood and are rapidly transported throughout the body g They work by destroying particular parts of the host s cells or by inhibiting certain metabolic functions h Highly specific in their effects on body tissues i Disease specific j The body produces antitoxins that provide immunity to exotoxins k Toxoids altered exotoxins from inactivation from heat or by chemicals such as formaldehyde or iodine i Naming Exotoxins 1 Exotoxins are divided into three principle types on the basis of their structure and function A B toxins
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