Antibacterials Flashcards
Define bacteriostatic
Prevents growth and replication
Define bactericidal
Kills bacteria
Explain the differences between bacterial and eukaryote cell walls
Bacterial = rigid
Eukaryote = semi-permeable membrane
Name 3 mechanisms of acquiring resistance genes
- conjugation
- transduction
- transformation
Explain the conjugation method of acquiring resistance genes
Where two bacteria exchange genetic information between themselves - can pass on resistance genes
Explain the transduction method of acquiring resistance genes
Genetic material is exchanged between bacteria using a virus (a phage - virus specific to bacteria)
Explain the transformation method of acquiring resistance genes
Bacteria pick up exogenous DNA from the environment
Bacterial cell wall is made up of what?
Peptidoglycan - a sugar backbone unique to bacteria
Transpeptidase is also known as?
Penicillin binding protein
MOA of B-lactam antibiotics?
They form a covalent bond with transpeptidase which interferes with the synthesis of the cell wall by preventing the cross linking of peptidoglycan chains that is facilitated by transpeptidase
Name 2 mechanisms for resistance for B-lactam antibiotics
- enzymatic degradation - bacteria acquires a b-lactamase enzyme which degrades the drug
- altered receptor - bacteria acquires a new version of transpeptidase which does not bind to drug
True or false: cephalosporins are fungi-derived
True
Is cefalexin susceptible to degradation by B-lactamase
Yes
Vancomycin MOA?
Interferes with cell wall synthesis. Binds to the end of the D-Ala-D-Ala sequence which prevents transpeptidase from binding and forming a cross link.
Mechanism for resistance against vancomycin?
Altered receptor = The bacteria can change the D-Ala-D-Ala into D-Ala-D-Lac. This prevents vancomycin from binding, however can still bind to transpeptidase
Example: VRE
Explain the cell wall of TB
TB is a mycobacterium. This means it’s cell wall is largely made up of mycolic acid. This specialised cell wall is what prevents the mycobacterium from being killed by macrophages
Isoniazid MOA and indication?
A TB drug
Prevents the synthesis of mycolic acid
I.e. interferes with cell wall synthesis
Isoniazid mechanism of resistance?
Isoniazid typically gets converted into active form by the mycobacterium catalase enzyme which is encoded by the katG gene. Mutations in this gene prevent the formation of this enzyme, preventing the activation of the drug
Explain what a granuloma is
A granuloma is a cluster of TB living inside immune cells. The TB is dormant in the granuloma
What could cause a granuloma to become active
If the patient becomes immunocompromised
Explain the MOA of rifampicin
Blocks RNA synthesis by inhibiting bacterial RNA polymerase - blocks transcription
By blocking RNA synthesis, you are preventing the formation of proteins essential for replication
Discuss the resistance for rifampicin
Develops rapidly.
A mutation in the gene that encodes for the RNA polymerase causes a change in the B subunit that the drug binds to.
Need to use rifampicin in combination therapy
Name 2 drugs that are folate synthesis inhibitors
Trimethoprim and a sulfonamide (like sulfamethoxazole)
Why would inhibiting folate synthesis be a good mechanism for anti bacterial drugs?
Because the folate is required for DNA and RNA synthesis in bacteria.
It is specific to bacteria because they synthesise their own folate, whereas humans get it from their diet
DHFR stands for?
Dihydrofolate reductase
MOA of sulfonamides?
Structural analog for PABA (p-aminobenzoic acid) which is a precursor to folic acid. Drug competes with PABA for binding to an enzyme. Reduces the production of folic acid
MOA of trimethoprim?
A competitive antagonist for DHFR, which typically converts folic acid into dihydrofolate (more active form)
How do sulfonamides and trimethoprim work synergistically?
Sulfonamides reduce the production of folic acid, meaning there is less folic acid for trimethoprim to compete with for binding to DHFR
Explain how the bypass mechanism of resistance reduces efficacy of trimethoprim
The bacteria increases concentration (upregulates) of DHFR enzyme. More receptors available = less effective competitive antagonist
Which drug class can cause SJS?
Sulfonamides
Explain how some bacteria are instrinsically resistant to sulfonamides
They do not need PABA to make their folate
Is isoniazid a prodrug?
Yes
DNA gyrase is also known as?
Topoisomerase II
Is topoisomerase IV more common in gram negative or positive bacteria?
Positive
Which topoisomerase enzyme relieves concatenation?
IV
Which enzyme relieves supercoiling?
Topoisomerase II
Ciprofloxacin belongs to which class of drugs?
Fluoro-Quinolones
Name a fluoroquinolone
Ciprofloxacin, norfloxacin
MOA of fluoroquinolones?
Inhibits topoisomerase II and IV. Binds to the alpha and beta subunits of the enzymes to prevent them from re-sealing the DNA
Action of topoisomerases?
They cut, then re-seal DNA strands when supercoiled or concatenated
Name 1 resistance mechanism for the fluroquinolones
-mutation in alpha subunit reduces binding affinity
- a plasmid-encoded protein binds to topoisomerase and protects it
- norA gene is acquired which encodes for an efflux pump for the drug
Which bacteria are intrinsically resistant to metronidazole and why?
Aerobic bacteria. This is because they lack the enzyme required to activate the drug
MOA of metronidazole?
Once activated, the drug is chemically reactive and causes damage to the DNA. It damages the DNA faster than it can be repaired, leading to accumulation and cell death
Role of the pyruvate:ferredoxin oxidase enzyme?
Responsible for converting metronidazole into its active form
Discuss the reaction between metronidazole and alcohol
Metronidazole inhibits the aldehyde dehydrogenase enzyme - the enzyme responsible for breaking down alcohol.
Mechanisms for resistance in metronidazole?
- mutations in the pyruvate:ferredoxin oxidase enzyme (needs this enzyme to be activated)
- over expression of the gene (RecA) that encodes the protein responsible for DNA repair
Name 3 classes of protein synthesis inhibitors
Aminoglycosides, macrolides, tetracyclines
(MAT)
Which class does gentamicin belong to?
Aminoglycoside
Why is gentamicin more effective on aerobic bacteria?
It’s uptake is oxygen dependent
Which class of drugs are cationic?
Aminoglycosides
What effect do cationic drugs have on bacteria?
They bind to the anionic bacteria membrane and disrupt it. This allows leakage of intracellular contents and increased drug uptake through the pores
Gentamicin can be combined with which drugs for a synergistic effect?
Cell wall drugs (like b-lactams)
Due to cationic effect
MOA of aminoglycosides?
Bind to the 30S subunit and prevent elongation step of protein synthesis. Also causes misreading of mRNA - causing abnormal protein production
Resistance mechanism for gentamicin?
- alteration to 30S subunit to prevent binding
- acquisition of an enzyme that can degrade the drug
Name a macrolide
Erythromycin or clarithromycin
Name a lincosamide
Clindamycin
MOA of macrolides?
Bind to the 50S subunit of the ribosome and prevent translocation step of protein synthesis
Resistance mechanism for macrolides?
- alteration to 50S subunit
- acquisition of an enzyme that degrades the drug
- increased expression of efflux pumps
Name 2 tetracyclines
Tetracycline and doxycycline
MOA of tetracyclines?
Binds to 30S subunit of ribosome and prevents tRNA from binding which blocks protein synthesis
Why do tetracyclines cause issues with bones and teeth?
They bind to calcium
MOA of mupirocin?
Prevents the amino acid isoleucyl from joining the growing protein chain. Causes production of the incorrect protein.
Types of bacteria gentamicin is effective against?
Gram negative and aerobic (uptake into cell is oxygen dependent)
