33. Bacterial Pathogenesis Flashcards
In the small intestine; cholera toxin acts by
- ADP–ribosylation of Gs which makes it constitutively active which results in phosphorylation and activation of CFRR channels
- Oversecretion of Cl- ions from the enterocytes
- Na+ and H2O follow Cl- into the gut lumen; this ionic imbalance causes watery diarrhoea
- Pathogen can then be transmitted through the faecal-oral route
The Gram negative cell wall component that causes septic shock is:
- Lipopolysacharide
- O antigen
- Core oligosacharride
- Lipid A
Examples of superantigen
-
Toxic shock syndrome toxin 1 (TSST)
- Produced by staphylococus aureus
- TSST-1 binds primarily to alpha-class chain of MHC II
- Stimulating the release of large amounts of interleukin-1, interleukin-2 and tumour necrosis factor
-
Streptococus pyogenes toxin
- Produced by streptococus pyrogenes
- SpeB binds to beta-class chain of MHC II
- Stimulating the release of large amounts of interleukin-1, interleukin-2 and tumour necrosis factor
What is toxic shock syndrome?
- Rare but life-threatening condition caused by bacteria getting into the body and releasing harmful toxins
-
Caused by
- Release of IL1, IL2 and TNF
-
Septic Shock Syndrome Toxin 1
- Staphylococus aureus
-
Streptococcal pyrogenic exotoxin A
- Streptococus pyrogenes
-
Septic Shock Syndrome Toxin 1
- Release of IL1, IL2 and TNF
-
Symptoms
- Fever
- Rash
- Skin peeling
- Low blood pressure
-
Treatment
- IV antibodies
- Incision and driainage of abscesses
Which type of bacterial toxin is being described in the following sentence?
“These toxins indiscriminately activate T cells of the immune system causing system–wide inflammation and other serious; potentially fatal; symptoms.”
- Superantigen/Endotoxin
- Released during cell lysis
- Toxic shock syndrome toxin 1
- Staphylococus aureus
- Streptococcus pyogenes toxin
- Streptococcus pyogenes
- Exotoxin
- Released during:
- Cell lysis
- Secreted
- Examples
- Botulinum toxin by clostridium botulinum
- Diptheria toxin from corynebacterium diptheria
- Released during:
What does acid fast mean?
- Acid fast
- Organisms can resist the acid and/or ethanol-based decolorization procedures common in many staining protocols
- E.g. Myobacteria
What structure is associated with the bacterial cell wall of certain strains of Streptococcus pneumoniae prevents phagocytosis?
-
Capsule polysaccharide
- Capsule is antiphagocytic
What is peptidoglycan polymer composed of?
- Alternating units
- N–acetylmuramic acid
- N–acetylglucosamine sugars
- Linekd by short peptides
A lipid found in high concentration in the cell wall of acid–fast bacteria. What are the other components found in the cell wall of acid-fast bacteria?
- Mycolic acid
- Mycolic acid wall structures
- Mycolic acid
- Peptidoglycan
- Arabinogalacta
Outer membrane protein that regulates the access of small hydrophilic molecules into the cell.
Porin
A phospholipid that is responsible for the toxic effects of endotoxin
- Lipopolysaccharide
- Specifically Lipid A
- (NOT O-antigen or core oligosaccharide)
- Specifically Lipid A
A protein filament that facilitates the attachment between bacterial cells during conjugation.
Sex pilus
A thick polysaccharide layer that can inhibit phagocytosis.
- Polysacharride capsule
- Used by streptococus pneumonia
A polymer of glycerol phosphate or ribitol phosphate that is present in the cell wall of Gram-positive bacteria
Teichoic acid
A whip–like; protein filament that projects from the cell surface and plays a key role in locomotion.
Flagellum
A major constituent of the outer membrane of Gram negative bacteria; that activates innate immunity through Toll–like receptor–4.
Lipopolysaccharide
A non–reproductive structure formed by some Gram positive bacteria; that enables the bacterium to withstand long periods of environmental stress
- Endospore
Give six different targets within bacteria that are sufficiently different from host cells to be used as antibiotic targets. In each case, give an example of a relevant antibiotic (or class of antibiotics).
-
(DD–)Transpeptidase (structural)
- Penicillin (beta–lactam)
- Cephalosporins
-
Blocks bacterial RNA polymerase (transcription)
- Rifampicin (rifamycins)
-
Inhibit synthesis of 50s ribosome subunit (translation)
- Erythromysin (macrolide) prevents A–>P
-
Inhibits 30s ribosome subunit (translation)
- Gentamycin (aminoglycoside) - acceptance of incorrect AA-tRNA complexes
- Tetracyclin - blocks A site
-
Inhibits folic acid synthesis by inhibiting dihydropterate synthetase (replication)
- Sulfonamids
-
Inhibits folate synthesis by inhibiting dihydrofolate reductase (replication)
- Trimethoprim (diaminopyridines)
-
Inhibits topoisomerase IV and DNA gyrase
- Ciprofoxacin (fluoroquinolines)
- For gram positive bacteria, topoisomerase IV is the target
- For gram negative bacteria, DNA gyrase is the target
- RNA polymerase = converting DNA into RNA (transcription)
-
Prokaryotic ribosome
- 50S and 30S (70S total)
-
Eukaryotic ribosome
- 60S and 40S (80S in total)
Penicillin
- A beta–lactam that inhibits DD transpeptidases to prevent the production of peptidoglycan;
- Peptidoglycan = component of the bacterial cell wall
-
Bactericidal
- Can only act when cells are growing and synthesising
-
Broad spectrum infections
- Skin infections
- Chest infections
- Urinary tract infections
Describe erthromycin. What bacteria can it treat?
- Macrolide
- Binding reversibly to the 50s subunit to inhibit protein synthesis
- Preventing release of tRNA after it has transferred its AA to the new peptide chain
- Preventing aminoacyl translocation from A site to P site (APE)
- Preventing release of tRNA after it has transferred its AA to the new peptide chain
- Bacteriostatic
- Treates chylmadia
Gentamycin - what is it and what does it treat? What are its potential side effects?
- Aminoglycoside
- Binds to the 30s subunit to inhibit initiation complex and misreading of mRNA to occur (Bacteriostatic)
Gram negatives (but can be used for broad spectrum)
- Potential toxic effect on:
- Kidneys
- Vestibulocochlear nerve (VIII)
EGMA
Trimethoprim - what is it and what does it treat?
- 2,4–diaminopyridine
- Inhibits folate synthesis by binding to dihydrofolate reductase
- Bacteriostatic
’
- Urinary tract infections
- E. Coli
- Proteus mirabailis
- Klebsiella E.coli
- Enterobacter
- Pneumocystis pneumonia
Rifampicin - what is it and what does it treat?
- Inhibits bacterial RNA polymerase
- Prevents elongation of the 5’ end of the RNA transcript past more than 2 or 3 nucleotides
- Prevents transcription
- Part of the rifamycin family
- Tuberculosis
An antibiotic that disrupts DNA synthesis by inhibiting DNA gyrase
Ciprofloxacin (quinolone)
An antibiotic that inhibits peptidoglycan cross–linking by binding to the D–alanyl–D–alanine end of the pentapeptide and which is NOT degraded by β–lactamases
Methicillin
An antibiotic that inhibits protein synthesis by blocking binding of tRNA to the acceptor site on the 30S ribosome
- Tetracyclin
- Another aminoglycoside
- Tetracyclin blocks binding of the A site
- Gentamycin results in acceptance of incorrect AA-tRNA complexes
- Ribosome synthesises the wrong amino acids throughout
- 1 in 500
- Misfolded amino acids eventually lead to the wrong structure
EGMAT
An antibiotic that inhibits protein synthesis by blocking the peptide binding site on the 50s rRNA
- Erythromycin
- Part of the macrolides
-
Tetracycline
- Blocks A site
- Prevents charged aminoacyl-tRNA from binding
-
30 S
-
Gentamycin
- Part of the aminoglycosides
-
Gentamycin
Anti-bacterial agent that inhibits the synthesis of folic acid
-
Sulfanomides
- Bind to dihydropterate synthetase
- Preventing conversion of dihydropterate disphosphate + para-aminobenzoic acid (PABA) --> dihydropteroic acid
-
Trimethorpim
- Binds to dihydrofolate reductase
- Preventing conversion of dihydrofolic acid into tetrahydrofolic acid
Op = S(pec)
An antibiotic that inhibits peptidoglycan synthesis and which is degraded by β–lactamases
- Penicilin
- Cephalosporin
A beta lactam antibiotic that inhibits bacterial cell wall synthesis
- Pencillin family
- Amoxicillin
- Phenoxymethylpenicillin
- Methicillin
- Benzypenicllin
- Flucloxacillin
- Carbapenem
- Cephalosporins
Which antimicrobial drugs interfere with folate metabolism?
- Sulfonamides
- Trimethoprim
- Part of the diaminopyramidines
A macrolide antibiotic that blocks protein synthesis by binding to the 50S subunit of bacterial ribosomes
- Erythromycin
- EGMA*
The most common mechanism of resistance to quinolones such as ciprofloxacin is through:
- Alterations in the target enzymes
- Topoisomerase IV
- DNA gyrase
- Reduced drug entry
- Increased drug efflux
Resistance to tetracycline is often mediated through
- Tetracycline efflux
- Ribosomal protection
An 18 year old woman presents with an acute sore throat. On examination; she has severe inflammation of the tonsils. A swab of the affected area is cultured and the resultant organisms appear to be roundish; in short chains and purple after Gram’s staining.
- What is the most likely causative organism (Genus and species)?
- What would be the likely result of the catalase test?
- Name two virulence determinants of the organism.
- Is the infection likely to be readily controlled by penicilliin?
-
Streptococcus pyogenes
- Gamma haemolysis
- Lancefield Type
- Catalase negative
- Antiphagocytic structures
- M protein
- Hyaluronic capsule
- Yes, penicillin will be effective as there is no beta-lactamase activity
What is the molecular basis of the pathogenesis of E. coli?
-
Heat labile toxin( LT):
-
ADP–ribosylation of Gs CFTR
- irreversibly activates adenylyl cyclase on CFTR
- Increases cAMP which activates kinases that phosphorylation transporters in the membrane
- The transporters export ions thus causing fluid; Cl– and K+ to move out into lumen)
- Results in watery diarrhoea
- Cholera toxin has same action
-
ADP–ribosylation of Gs CFTR
What does the pink colour of the colonies on MacConkey’s agar indicate?
Lactose–fermenting
Yellow = non-lactose fermenting
Gram negative bacteria are more likely to display intrinsic resistance to beta lactam antibiotics than Gram positive bacteria T/F)
T
A 10–year–old girl suddenly developed a moderate fever and severe sore throat. On examination; her temperature was found to be 39C; her cervical lymph nodes tender and swollen and her tonsils to be inflamed; with whitish patches. The GP took a throat swab for microbiological culture on blood agar and; when the results came back the following day; prescribed penicillin. The symptoms began to ease within 24 hours and were fully resolved within a week.
- What would you expect to be the appearance of the colonies on blood agar?
- What would you expect the microscopic appearance of these organisms to be following Gram staining?
- What confirmatory test might be used and what would be its expected result?
- What human cells would predominate in the white patches seen in the throat?
- Name one potential disease sequela that is avoided by antibiotic treatment.
Streptococcus pyogenes
- Cocci in chains
- Clear zone around colonies (beta–haemolytic), purple (gram positive)
- Catalase – negative/Lancefield typing A
- Neutrophils
- Rheumatic fever or acute glomerulonephritis
How can laboratory tests on bacterial cultures differentiate the following? For each pair; name a critical test and the expected results:
- Staphylococcus from Streptococcus
- Staphylococcus aureus from common;non–pathogenic Staphylococci
- Streptococcus pyogenes from other Streptococci
-
Catalase
- Staphylococcus = positive
- Streptococcus = negative
-
Coagulase
- Staphylococcus aureus = positive
- Non–pathogenic Staphylococci (staphylococcus epidermis) = negative
-
Lancefield typing
- Streptococcus pyogenes = beta haemolysis (complete) & Lancefield type A result
Which non–motile Gram negative bacterium grows as rods and cannot be cultured on MacConkey agar plates
Haemophilus
Which non–spore forming Gram negative pathogen commonly found on mucosal surfaces grows as a diplococcus with adjacent sides flattened?
Neisseria