Bacterial multiplication and survival in the host Flashcards
a) How some bacteria survive and spread in the extracellular environment
b) how some bacteria spread inside host cells
a) Staphylococcus and Streptococcus (often called pyogenic cocci) use batteries of enzymmes to spreaf through tissues, eg collagenase to break down connective tissue, coagulase to induce fibrin clot formation, staphylokinase to break down blood clots, DNAse to break down DNA in pus
b) Some (eg Listeria) escape from the entry vacuole into cytosol. Intracellular movement and replication leads to intercellular spread. Movement involves more cytoskeletal rearrangement - actin polymerisation induced by the pathogen at one end (pole) of the bacterial cell
Others (eg Salmonella) stay in their entry vacuoles and replicate. Salmonella typhy (causes typhoid) then survives in macrophages and are spread locally and throughout the body by the host defence system
Example of chlamydia as an obligate intracellular pathogen
a) what diseases does it cause and overview of the bacteria
b) the intracellular develepment and replication cycle
a) Chlamydia trachomatis causes i) trachoma (most prevalent form of iinfectious blindness). ii) non-gonococcal urethritis (common STI and often asymptomatic, but can cause acute prostatitis - inflammation triggered by chlamydial LPS, and chronic infection can lead to pelvic inflammatory disease and infertility). Relatively small genome and has lost many metabolic enzymes and pathways, so must scavenge essential metabolites from host cell
b) Involves transition from an infectious elementary body (EB) - low metabolic activity and cannot replicate, to a reticulate body (RB) that replicates inside host cells.
EB attaches to host epithelial cells and induces uptake in endosome, involving rearrangement of host actin cytoskeleton by chlamydial effector Tarp that is injected into the host cell using a virulence needle. EB in endosome differentiates to RB which replicates, and RB-containing vacuole segregates from normal endosome maturation pathway and becomes a protective, nutrient-rich vacuole/inclusion. RBs produce both EBs and RBs. Host cell lyses to release EBs that go on to infect more host cells, causing damage by cell lysis and inflammation triggered by chlamydial LPS
Host defences (list physical and chemical barriers and how)
Skin - dry acidic, cool and high salt to limit growth. Sloughing cells to remove bacteria
Mucous membranes - cilia in pulmonary airway, eyelid blinking, urine flow, GI tract motility. Mucin layer (a physical barrier to trap bacteria). Tight junctions to limit invasion between cells
Gastric acid and bile salts - inhibit growth
Lysozyme - in tears to split bacterial peptidoglycan
Iron limitation - sequestraction by lactoferrin and transferrin
Resident microflora - some sites densely occupied like the colon, inhibits colonisation by occupancy. Toxic waste produced (pH) and chemicals (fatty acids, bacteriocins)
Host defences (early immunne and induced immune responses)
Early immune - acute inflammation. Complement (alternative pathway activated by bacteria eg LPS). Macrophages bind bacteria via lectins, kill in phagolysosomes
Induced immune - enhanced inflammation. Classical pathway of complement activation. Ig produced (CD4/MHCII/Th2). IgG opsonisation (Fc-mediated phagocytic killing). Ig neutralisation if toxins. IgA at mucosa to stop colonisation. Additional macrophage activation by MHCII/Th1
Evasion of host hostile environment
a) overcoming lack of essential iron
b) overcoming stomach acid
a) virtually all pathogens bind iron at a high affinity (much higher than host) by secreting iron-binding siderophores and reimporting them back into the cell when loaded. eg green fluorescent pyoverdin is secreted by the opportunistic pathogen Pseudomonas aeruginosa. eg equibactin produced by Streptococcus equi. Means even is iron is sequestered by host, they can still access enough
b) pathogens like Shigella (causes dysentery) and Helicobacter (causes stomach ulcers) can resist low pH by pumping H+ out of their cell and/or producing NH3 by urease action
How bacteria prevent uptake by macrophages (4 ways)
Paralyse the macrophage by subverting its finctions: Involves disrupting intracellular trafficking and signal transduction by injecting anti-phagocytic proteins into the macrophage, eg Yersinia injects multiple effectors including YopT (a protease that targtes small GTPases to disrupt the cytoskeleton) and YopP (an acetyl transferase that inhibits signalling, triggering apoptosis)
Inhibit chemotaxis: cleaving complement C5a with a C5a peptidase
Resist phagocytosis by shielding with antiphagocytic capsules: capsules commonly made of polysaccharide, eg bacteria causing pneumonia like Streptococcus pneumoniae. Capsule prevents phagocytosis by steric hindrance (physical block), displaying a non-immunogenic polysaccharide like sialic acid, or lacking affinity for complement factor B, so C3b isn’t formed
Kill macrophages with secreted cytolysins: Pore-forming toxins that disrupt cell functions, cause apoptosis, and destroy cell membrane integrity. Produced by many pathogens, eg Streptococcus pyogenes (produces spreptolysins O and S), bacteria causing pneumonia (produces pneumolysin), as well as E. coli and B. pertussis.
a) How bacteria can survive inside macrophages
b) How bacteria resist complement
a) Interfere with phagosome maturation. Faculative intracellular pathogens like Salmonella and Mycobacterium inhibit phagosome-lysosome fusion. The same pathogens also survive phagolysosome onslaught by resisitng the oxidative burst
In Leigionnaires’ disease, Leigionella pneumophila multiplies in alveolar macrophages. Prevents the oxidative burst by modifying the host phagosome with bacterial proteins that block lysosome fusion. This stimulates cytokine release, and lung damage reflects a vigorous inflammatory response
b) LPS O-antigen and capsules contribute to serum (complement) resistance by hindering access to the bacterial cell, preventing formation of membrane attack complex
How bacteria evade antibody recognition (3 ways)
Mimic host: covalently attaching sialic acid to LPS, eg Neisseria gonorrhoea, Neisseria meningitidis
Shut off or switch expression of surface antigens by phase variation: Rearrangement of an invertible promotor region, flanked by recombination sequences recognised by site-specific DNA recombinase, eg Salmonella flagellin
More complex DNA recombination to generate antigenic variation: Silent (non-expressed) pilin genes, encoding antigenically distinct pilin proteins, recombine into a transcriptionally active expression locus, eg in Neisseria
How bacteria can inactivate antibodies (2 ways)
Cleave secretory IgA: ANtibody cleavage by specific proteases of mucosal pathogens like Streptococcus pneumonia, Haemophilus influenzae, Neisseria gonorrhoea, Neisseria meningitidis
Bacteria bind to Ig Fc component
Multifactorial virulence by
a) Streptococcus pyogenes (+ what does it cause)
b) Streptococcus equi
a) Lancefield group A Causes erysipelas, impetigo, mastitis, pharyngitis and other acute infections (tonsillitis, scarlet fever, puerperal fever, necrotizing fasciitis. Produces multiple virulence factors that aid colonisation, spread and evasion of host defences:
Colonisation of epithelium - numerous adhesins
Spread, survival and damage - polysaccharide capsule. Surface M protein has 80 serotypes (antigenic variation) and binds complement factor H. C5a peptidase to inhibit chemotaxis. Streptolysins O and S, pore-forming toxins (β-haemolysins). Pyogenic toxins, superantigens (can cause toxic shock syndrome). Hyaluronidase (breaks down tissue). Streptokinase (lyses clots). DNAse depolymerises DNA in pus to reduce abscess viscosity.
Acute inflammatory infection can lead to later complications: Rheumatic fever (heart and joint granulomas, plus fever, can lead to rheumatic heart disease. Believed to involve autoimmunity eg to M protein), Glomerulonephritis (accumulation of Ab-Ag complexes that lodge in kidney glomeruli to cause inflammation - type III hypersensitivity)
b) Lancefield Group C. Pathogen of horses that causes the highly contagious disease strangles, causing purulent nasal discharge and abscesses in the lymphnodes of the head and neck.
Infection can become systemic (bastard strangles) with bacteria spreading via lymphatic system. Later complications can include myocarditis.
Has similar virulence factors to Strep. pyogenes and a specific iron-binding siderophore, equibactin
