PATHOGENIC EFFECTS OF BACTERIA H.A. MWAKYOMA

PATHOGENIC EFFECTS OF BACTERIA Extracellular bacteria Intracellular bacteria Extracellular bacteria:- examples Staphylococcus aureus Pneumococci Gonococci (Neisseria gonorrhoea) Clostridium tetani perfringence botulinum

Extracellular bacteria:- examples :- examples Salmonella sp Vibrio cholerae Shigella sp Gram –negative bacteria Klebsiella pneumoniae E. coli Pseudomonas sp. etc

Extracellular bacteria:- Extracellular bacterial pathogens of man resist early engulfment (phagocytosis) by neutrophils in order to gain a foothold in the host tissue for effective mechanism to favour their survival (ability to resist phagocytosis) Bacteria may resist phagocytosis in a number of ways: Generation of toxins; Some bacteria generate toxins lethal for leucocytes and their host cells

Bacteria may resist phagocytosis in a number of ways: Forming slipperly hydrophilic capsules Other bacteria solve their survival problem by forming slipperly hydrophilic antiphagocytic capsule- e.g. pneumococci that resist attachment to wondering neutrophils. Some bacteria resist phagocytosis by the presence of M- protein and hyluronic acid- in Streptococci pyogens

FALCULTATIVE INTRACELLULAR BACTERIA- direct damage Some organisms like Tubercle bacilli and other chronic infectious agents counteract phagocyte aggression after being interiorized by the following mechanisms:- Inhibiting fusion of phagocytic vacuoles with lysosome Shielding (Evading) themselves from the free radicals and enzymes generated around them, hence cannot leave the phagosome. They have the potential of establishing latent foci of infection capable of long-term reactivation often resulting in granulomatous lesions Bacterial survival in the face of effective phagolysosome fusion is attributed to specific surface components:-

TB mechanisms- cont-- Mycocydes Covalently linked complex lipids and carbohydrates Appear to be directly related to bacterial virulence Sulfated glycolipids (sulfatide) Prevents the fusion of phagosome with lysosome and favours the intracellular survival of Mycobacteria within macrophages The lipid fraction contributes to virulence and to the sensitivity state associated with tuberculosis The emergence of hypersensitivity reaction to the tubercle bacilli plays a dominant role in the tissue destruction encountered in this disease.

FALCULTATIVE INTRACELLULAR BACTERIA Having established themselves, bacteria can damage host tissues directly or indirectly in a number of ways- mechanism of bacteria-induced injury. This can be done by; Bacterial adhesins and Toxins/ Enzymes(Aggressins)

BACTERIAL TOXINS Bacterial toxins are divided into; Those that are liberated from multiplying bacteria (Exotoxins) and Those that are associated with the cell wall and are released after death of the bacterium (Endotoxins)

EXOTOXINS ACTIONS: Bacterial exotoxins appear to work in two main ways: In the form of cytolytic toxins which can alter cell permeability As Bipartite toxins that bind to a receptor with one portion, allowing the release of the other portion into the host cytoplasm.

ACTIONS of EXOTOXINS Bipartite exotoxins are actually activated by enzyme cleavage within the host target cell, e.g. diphtheria, cholera.

EXOTOXINS Most are produced by gram-positive bacteria They are proteins A few are specific enzymes (Aggressins) When liberated locally they can cause local cell and tissue damage Those that damage phagocytic cells are particularly useful to the microorganism Those that promote the spread of bacteria enter the blood and cause generalized toxic effects

EXOTOXINS Clostridium perfringens: Clostridium perfrigens atoxin Is a phosphalipase – acts on cell membrane May cause; Cell necrosis Haemolysis toxaemia

EXOTOXINS Clostridium tetani toxin: Blocks the action of inhibitory neurones Causes; Overaction of motor neurons Muscle spasms Lockjaw

EXOTOXINS Corynebacterium diphtheriae toxin: Has Bipartite toxins that bind to a receptor with one portion, allowing the release of the other portion into the host cytoplasm Inhibits cell protein synthesis Heart damage Nerve paralysis Shigella dysenteriae enterotoxin (neurotoxin): Induces fluid loss from intestine and Induces vascular endothelial damage in brain Causes diarrhoes and neurological disturbances

EXOTOXINS Vibrio cholerae enterotoxin: Has Bipartite toxins that bind to a receptor with one portion, allowing the release of the other portion into the host cytoplasm Activates adenyl cyclase, and raises CAMP level in cells Acts on intestinal epithelial cells Causes water and electrolyte loss into the intestine

EXOTOXINS Bacillus anthracis complex: 3 factors form a toxic complex and cause; Increased vascular permeability Causing oedema and haemorrhage (primary lesion) and Circulatory failure (systemic disease)

EXOTOXINS Clostridium botulinum toxin: Blocks release of acetylcholine, leading to; Neurotoxic signs paralyses

EXOTOXINS Streptococcus pyogenes erythrogenic toxin: Causes vasodilation Streptococcus leucocidin and streptolysins: These kill phagocytes- antiphagocytic activity Streptokinase – lyses of fibrin This is an aggressin – which is a bacteria enzyme which alter the local environment to the benefit of the organism Hyaluronidase – liquifies connective tissue matrix These two, promote spread of bacteria in tissue

EXOTOXINS Staphylococcus aureus atoxin: Cytotoxic, Action on cell membranes – causes necrosis at the site of infection; systemic toxicity Staphylococcus aureus leucocidin – kills phagocytes, thus is antiphagocytic Staphylococcus aureus enterotoxin Acts on vomiting centre in brain- causing nausea, vomiting, diarrhoea (food poisoning)

ENDOTOXINS These form part bacterial cell wall The word endotoxin generally refers to the complex phospholipid-polysaccharide –protein complex macromollecules associated with cell wall The lipopolysaccharide (LPS) is the important important component LPS is commonly found in gram-negative bacteria

ENDOTOXINS The LPS of gram-negative bacteria consists of 3 components; A core polysaccharide common to many gram-negative bacteria, An O specific polysaccharide which confers virulence and serological specificity on the macromolecule and A lipid A component manly responsible for toxicity Endotoxins are also pyrogenic

Bacterial adhesins Some strains of bacteria e.g. E.coli and Neisseriae have found to have hair-like filaments or fimbriae which assist them to attach themselves to body surfaces, with obvious survival benefits to these particular strains