We - WG: Literature assignment, cross presentation Flashcards
In which way is isoniazid bactericidal?
To rapidly diving mycobacteria
In which way is isoniazid bacteriostatic?
To slow dividing mycobacteria
By which enzyme is isoniazid activated?
KatG
How does isoniazid lead to cell death? (explain complicated)
Isoniazid is activated by KatG, and then interacts with NADH in presence of InhA. Then it inhibits InhA activity which decreases mycolic acid synthesis, and causes disruption of the outer membrane function and cell death.
Why is the dose of Isoniazid higher for tb meningitis?
Because isoniazid needs to cross the blood brain barrier
What method of resistance for isoniazid does tb have? (2) (explain complicated)
Presence of a variant in the KatG gene in codon 315. Also presence of InhA mutation.
Which enzyme does Moxifloxacin inhibit?
DNA gyrase enzyme
How does moxifloxacin lead to tb cell death? (explain complicated)
Binds to the gyrase-A sire, forms a drug enzyme DNA complex which blocks replication, causes chromosomal fragmentation resulting in cell death.
Against which type of tb cells does moxifloxacin work especially well?
Persisting cells
What is the resistance mechanism in tb for moxifloxacin? (explain complicated)
Chromosomal mutations that lead to GyrA codons or GyrB codons that cause an increased minimal inhibitory concentration (MIC).
Why doesn’t moxifloxacin work 100%? (explain complicated)
Because of necrotizing granulomas. The moxifloxacin goes to the lung and goes to the granuloma, but doesn’t like to be in the necrotizing part of the granuloma, where most of the bacteria are.
Which kind of antibiotic is bedaquiline?
A diarylquinolone
What is the working mechanism of bedaquiline for tb? (explain complicated)
Inhibits bacterial ATP synthase by inhibiting the proton pump. In doing so it induces bacterial cell death.
What are the two possible resistance mechanisms in tb for bedaquiline? (explain complicated) (2)
Mutations in atpE, Rv0678 genes.
AtpE gene encodes a subunit of ATP-synthase in TB, and the mutation generates that subunit to have a lower affinity for bedaquiline.
Rv0678 gene encodes a repressor protein, which normally stops the bacteria from making efflux pumps that pump out the drug. In the mutation the repressor protein won’t bind, making it more active, meaning the drug gets pumped out more.
What is the working mechanism for rifampicin?
The target of rifampicin in bacteria is the β-subunit of the DNA-dependent RNA polymerase. Rifampicin interrupts the binding of the β-subunit with DNA, which uncouples the production of mRNA and results in the death of the organism.
