Requisites for Successful Growth

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Requisites for Successful Growth. Attachment Nutrition Survival from host defence Transmission. Virulence Factors. Factors which promote infection and which contribute to disease Studied with mutants Are multifactorial Consist of: Factors promoting colonization and invasion - PowerPoint PPT Presentation

Text of Requisites for Successful Growth

  • Requisites for Successful GrowthAttachment Nutrition Survival from host defence Transmission

  • Virulence FactorsFactors which promote infection and which contribute to diseaseStudied with mutantsAre multifactorialConsist of:Factors promoting colonization and invasionFactors which are pathogenic

  • Bacterial Virulence Factors I: AdherenceCapsules Pili Adhesins

  • CapsulesPresent in some gram negative and positive bacteria.May be composed of protein or polysaccharide layers.Is poorly antigenic and anti-phagocyticCan act as a barrier to toxic hydrophobic molecules such as detergents.Can promote adherence to other bacteria or cell surfaces

  • Bacterial Virulence MechanismsAdherenceInvasionBy-products of growth (gas, acid)ToxinsSuperantigenImmune evasionResistance to antibiotics

  • Pili (Fimbriae)Composed of subunits of pilin.Promote adherence to other bacteria or host.Synonyms: adhesins, lectins, evasins, aggressins.Fragile, often replaced.

  • AdhesinsAdherence mediated by lectin activity.Allow attachment to vulnerable membranes such as surfaces of the respiratory, GI and urogenitary tract as well as dentine.Can alter structural properties of host cell membrane by signal transduction and induction of actin rearrangement (EPEC intimin) to enhance binding.

  • Bacterial Virulence Factors I: InvasionInvasins e.g. Yersinia Host cell necrosis e.g. Diphtheria toxin

    Promote phagocytosis e.g. Shigella

  • Bacterial Virulence Factors II: Iron AdsorptionSiderophores

  • ToxinsToxic byproducts of bacterial growth e.g. acids, gas, proteasesToxinsEndotoxins e.g. LPSExotoxins e.g AB toxinsToxins vs ToxoidsHeat labile vs Heat resistantIneffectiveness of antibiotics

  • ExotoxinsAB. e.g. Shigella dysenteriae, C. tetani, V. cholerae. Cell Membrane Disruption. e.g. C. perfringens Superantigens. e.g. S. aureus

  • Exotoxins I: AB (i)

  • Exotoxins I:AB (ii)

  • Exotoxins I: AB (iii)

  • Toxic Shock Syndrome

  • Endotoxins: LipopolysaccharideFeverLeukopenia, followed by leukocytosisComplement activationThrombocytopeniaCoagulationDecreased blood circulationShockDeath

    Invasins

    After ingestion and passage through the stomach, Salmonella organisms are able to invade and replicate in the cells lining the lumen of the small intestine. The adherence of the bacteria to the microvilli on the cell surface stimulates the rearrangement of actin (ruffling) with subsequent engulfment of the bacteria within endocytic vesicles. The bacteria remain in the vesicles and replicate until the cell is lysed.

    Host gene modification: p4 Module 2. Intimin of enteropathogenic E coli. An outer membrane protein which facilitates stronger attachment to epithelial cell surface following loose attachment via pili. Another bacterial protein called Tir is inserted into host cell membrane, which sets off a chain of signal transduction and enzymatic events resulting in a change in the surface structure of the cell making it easier for the bacterial cell to attach.For S. mutans, dextran and levan capsules are the means by which the bacteria attach and stick to the tooth enamel.

    Synthesis of the capsule takes energy and usually only occurs under conditions of environmental stress.Pili promote adherence to other bacteria or the the host. As an adherence factor (adhesin), pili are an important virulence factor for N gonorrhoeae and E coli.

    These attach to host cell receptors which are normally used for cell to cell contact or signal transduction. Attachment is usually via a protein at the tip of the pilus called a lectin which binds to specific sugar groups on the host cell receptors, such as mannose.

    Pili are extremely fragile and are often being replaced. Their structure is easily modified to escape recognition by antibodies and complementLectin - Proteins with ability to bind to sugars

    Adhesins confer ability to attach and colonize vulnerable membranes including intestinal, urogenital and bronchial epithelia and hard surfaces such as dentine. Some microbes can bind platelets and fibrin, permitting their deposition on heart valves which results in endocarditis (inflammation of the lining of the heart cavity).All pili are adhesins but not all adhesins are pili.

    Intimin is NB in EHEC and EPEC infections. After first adhering comparatively loosely to the intestinal epithelial cells by means of fimbrial adhesins, signal transduction events cause phosphorylation of proteins of the host cells as well as increasing levels of intracellular calcium and inositol triphosphates. This causes effacement of the microvilli. Intimin, which is an E coli outer membrane protein, causes intimate attachment of the E coli to the epithelial cells. As a result of the tyrosine phosphorylation of the host cell proteins, intimin can reorganize the cytoskeletal elements. In particular, filamentous actin forms cup-like pedestals directly beneath the bacteria.Although bacteria dont have mechanisms to enable them to cross skin, several bacteria can cross mucosal membranes and other tissue barriers to enter normally sterile sites and more susceptible tissue.

    These invasive bacteria either destroy the barruer or penetrate into the cells of the barrier. Shigella and Salmonella bind to tissue and initiate its destruction so they can invade the host.

    Enteropathogenic Yersinia organisms produce an invasin protein that promotes the binding of bacteria to cells, which in turn stimulates the cells to invaginate and take in the bacteria.Bacteria rely on host for iron to grow. Trouble is that very little free iron available. Most of it is intracellular within haeme, ferritin and other molecules. Extracellular iron is quickly sequestered by iron-binding glycoproteins such as transferrin (in serum) and lactoferrin (associated with secretions and PMN granules). Bacteria compete by secreting their own iron-binding chelators which can compete for this iron with the host.

    Alternatively, some bacteria can capture (hijack) host iron-chelator complexes directly. E.g. Neisseeria uses transferring-bound iron directly and Yersinia can use haeme. Listeria can remoc\ve iron from trtansferrin.

    The tissue destruction and lesions observed in syphilis are primarily the consequence of the patients immune response to infection.Blocks protein synthesis by inactivating EF-2 so preventing extension of nascent protein on ribosome.Cholera: Synthesizes AB toxin. Induces cAMP . This results in water loss and electrolyte leakage from cell.Teteanospasmin (an A-B toxin) is synthesized as a 151 000 Da peptide that is cleaved into a light (A chain) and a heavy (B chain) subunit by endogenous protease when the cell releases the neurotoxin. The two chains are held together by a disulfide bond. The carboxy terminal portion of the heavy chain binds to neuronal membranes. The light chain is then internalized and moves from the peripheral nerve terminals to the CNS by retrograde axonal transport. It is released from the postsynaptic dendrites, crosses the synaptic cleft and is localized within vesicles in the postsynaptic nerve terminals. Tetanospasmin acts by blocking the release of neurotransmitters (GABA) for inhibitory synapses, thus causing excitary synaptic activity to be unregulated )spastic paralysis). In contrast, C botulinum affects acetylcholine transmission which inhibits the release of excitatory neurotransmitters.resulting in death most commonly attributed to respiratory paralysisThe first outbreak of TSS occurred in 1928 in Australia, where the disease developed in 21 children, 12 of whom dies after an injection with S. aureus-contaminated vaccine. Fifty years later, in 1978, a doctor called Todd observed what he called toxic shock syndrome in seven children with systemic disease, and the first reports of TSS in menstruating women were published in the summer of 1980. This was followed by a dramatic increase in the incidence of TSS, particularly in women. Subsequently it was discovered that TSST-1-producing strains of S aureus could multiply rapidly in hyperabsorbent tampons and release toxin. The incidence of TSS dropped rapidly after these products were recalled.The disease is initiated with the localized growth of toxin-producing strains of S aureus in the vagina or a wound, followed by the release of the toxin into the bloodstraem. Clinical manifestations start abruptly and include fever, hypotension and a diffuse rash. Multiple organ systems (gastrointestinal, musculature, renal, hepatic, hematological, central nervous) are also involved, and the entire skin, including the palms and soles, desquamates.