Most bacterial pathogens cause damage both _______ by secreting _____, and _______ through the _____ ______ to their presence
directly, toxins, indirectly, host response
exotoxins can be denatured to produce _______ which are _____ ____ but still _______ and can be used for _______
toxoids, non toxic, immunogenic vaccination
Toxins can be split into two categories, _______ and ______ ______ _____
cytolysins, enzymatic intracellular toxins
Cytolysins target ______ ______ ______ and degrade the ______ _____ by ________. They can also be _____ _____ eg _____ _____ ______ ____
host cell membranes, membrane phospholipids, phospholipases, pore forming, strep pyogenes streptolysin O
Staph aureus produces a ____ ____ toxin called _____ toxin
pore forming, alpha
Low concentrations of cytolysins can _____ _____ ______ ______ which often leads to _______. At high concentrations they lead to _____ ____. The toxins can _____ _____ _____ and damage tissues to aid _____ _____
disrupt host signal transduction, apoptosis, cell lysis, disrupt immune cells, bacterial spread
Enzymatic intracellular toxins ______ host cells by _____ _______ _____. They have _____ ____ (B) and ____ (A) components. Often _____ _____ are cleaved into _____ ______ _____. They can also be _______. They enter cells via ______-______ ______ and _____
poison, specific catalytic activity, receptor binding, active, single polypeptides, catalytically active fragments, multimeric, receptor-mediated endocytosis, retrograde transport
ADP-ribosylating enzymes: eg _____ ____ and ______ _____. They add an ____ _____ group from _____ onto the target to change its _______. The targets are often ________ of ______ ______, so their action disrupts ______ ______. Diphtheria toxin targets ____
cholera toxin, diphtheria toxin, ADP ribose, NAD, shape, regulators, adenylate cyclase, signalling pathways, EF2, protein synthesis
Cholera toxin is the ______ ______ _______ of vibrio cholerae. It comes from a ________ and has integrated onto the ______ ______
key virulence factor, bacteriophage, bacterial chromosome
Cholera causes '_____ ____' _______ and the patient can lose up to ____ _____ per day. ____ _____ ______ reduces mortality from _____ to _____. The dehydration if untreated will lead to ______, ______ and sometimes _____ ____
rice water, diarrhoea, 20 lites, electrolyte replacement therapy, 50%, 1%, shock, collapse, cardiac failure
Vibrio cholerae colonises the _____ _____ _____, and adheres via ____ ____. Here they secrete _______ _____ _____. B subunits bind _________ ______ leading to _______-_____ ______ and _____ _____ to the _____. Here there is ________ of the A and B subunit
small intestine mucosa, pilus adhesins, multimeric cholera toxin, GM1-ganglioside receptors, receptor-mediated endocytosis, retrograde transport, ER, dissociation, translocate, cytosol, adenylyl cyclase, ADP-ribosylating, stimulatory G-protein, on, destabilisation, movement, ions, water
Diphtheria toxin: a _____ _____ ____ in _______. It is a _____ ______ carried on a ______ that has integrated into the ____ ______. It is regulated by transcription factor ______ which is a _______ when bound by ______. Once the bacterium is in the host a
key virulence factor, corynebacteria, viral gene, bacteriophage, bacterial genome, DTXR, repressor, iron, dissociates
Corynebacterium colonise the _____ ______ _____, causing _____ _____ _____ and _____ _____, due to its action preventing protein synthesis. The bacteria grow in the inflammatory exudate, forming a ________ which can eventually ______ the _____.
upper respiratory tract, intense local inflammation, mucosal damage, pseudomembrane, occlude, trachea
DTX is a _____ ______ _____ which binds to a _____ _____ _____ on the host cell, leading to ______-_____ ______. Host cell _____ cleave the DTX into its A and B fragments. The A fragment ______ to the ______ where it _____-______ ____ to shut off _____ __
single chain polypeptide, growth factor receptor, receptor-mediated endocytosis, furins, translocates, cytosol, ADP-ribosylates, EF2, protein synthesis
Bordetella pertussis and bacillus anthracis produce ______ ____ which ______ host cell _____ _____
adenylate cyclase, disrupt, ion balances
Shingella and EHEC produce _________ which ______ ____ ______ and block _______
glycosidases, depurinate 28S rRNA, translation
Clostridium difficile produces _______ ______ which modify small __-______, disrupt ________ and lead to large ______ ______ ______ and changes to ______ ______, allowing the bacteria to attach better to the membrane
glucosylating enzymes, G-proteins, signalling, actin cytoskeleton rearrangements, tight junctions
Salmonella typhi, E.coli and campylobacter produce _______ ______ _____ which _____ _____ and cause cell death
cytolethal distending toxins, cleave DNA
UPEC and meningitis produce _______ _______ ______ which ______ __-_____ to disrupt signalling and cause ______ ______ ______
cytotoxic nectrotising factors, deamidate G-proteins, actin cytoskeleton rearrangement
Tetanus toxin: produced during _______ _____ in ______ ______. The B chain binds receptors on ______ ______ _______, and the A chain is _______. It then ______ to the _____ where the TeNT protease _____ ______ _______ which blocks release of ______ and __
anaerobic growth, deep wounds, peripheral nerve membranes, internalised, translocates, CNS, cleaves SNARE synaptobrevin, inhibitors, neurotransmission, uncontrolled muscle contraction, spastic paralysis
Botulinum toxin: has the same ______ ______ as tetanus toxin but acts on _______ ______ to prevent the release of ________ / ________ at the _____. This results in ______ _______. This can be used clinically with extremely low concentrations - 'botox'
proteolytic action, peripheral nerves, neurotransmitter, acetylcholine, NMJ, flaccid paralysis
Advantages of producing enzymatic toxins: aid ________, aid ________, some are ________ but may kill animals to generate an ______ ______ _______. Some can _____ _____ _____ ______.
colonisation, transmission, incidental, anaerobic growth environment, subvert host cell function
Some toxins are _________ (SAg). Weakly interacting ______ and ______ are bound directly by Sag to bridge _____ _____ and _______. This leads to ______ of '_______' ___ ______ causing a _______ ______ and host _______. A good example is toxins produced by
superantigens, MHC, TCRs, T cells, APCs, activation, useless T cells, cytokine storm, damage, staphylococcus aureus, toxic shock syndrome
TSST secreted by S.aureus enters the bloodstream, causing _____ levels of ______: ____, ___ & _____. These lead to _____ _____ and ______
increases, cytokines, IL-1, IL-2, TNF, systemic shock, death
Advantage of superantigens: may _____ ______ ______. Excessive ______ disturb balance and may divert ___ _______.
deflect immune system, cytokines, T cells
Indirect damage: mainly from ______ _______: ie _____ _____, ____ _____ or in the _____ _____. ______ ___ overload can lead to ______ ______, and if inflammation crosses the BBB it can lead to __________
excessive inflammation, too much, too long, wrong place, lipid A, meningitis
Meningitis is _____ damage, it is _____ part of ______ ______. It is often caused by bacteria colonising the ___________ which enter the bloodstream to cause _________ which has potential to cross the BBB. If untreated meningitis is often fatal
accidental, not, bacterial survival, nasopharynx, bacteraemia
Common bacterial causes of meningitis are ______ ______, ______ _____ ___, __ _______ and _______ ________. Their capsules are ______ ______
neisseria meningitidis, haemophilus influenzae B, E.coli, streptococcus pneumoniae, weakly immunogenic
Chronic inflammation is rare in bacterial disease, but can be caused by ______ leading to ______ _______ _______. ______ ______ can also establish _______ infection leading to ______ ______ and _______.
chlamydia, pelvic inflammatory disease, helicobacter pylori, lifelong, gastric ulcers, cancer
Granulomatous inflammation can be caused by ________ ______ ________. ______ form _______ around the pathogen leading to _________. Mycobacterium ________ and ______ (treponema pallidum) also cause granuloma formation
persistent mycobacterium tuberculosis, macrophages, granulomas, fibrosis, leprae, syphilis
Other immunopathologies: ______-_______ ________ (a type III hypersensitivity reaction) and ______ _____ (LPS-induced inflammation and type III hypersensitivity)
post-streptococcal glomerulonephritis, Lyme disease
Other immunopathologies: bacterial antigens may contribute to ________ _______ (type II hypersensitivity reaction) eg _______ ____ ______ cross reactivity in ______ ______
autoimmune disease, streptococcal M protein, rheumatic fever
Chronic inflammation is rare in bacterial disease, but can be caused by ______ leading to ______ _______ _______. ______ ______ can also establish _______ infection leading to ______ ______ and _______.
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