Lecture 24 -- Antibiotics Flashcards
(29 cards)
- streptomycete metabolites
- DNA gyrase is the target
coumarins
- synthetic
- works against both gram negative and gram positive
quinolones
which type of antibiotic functions by binding to DNA gyrase – it affects the double-stranded cleavage/double strand religation equilibrium
results in accumulation of doubly cut DNA-GyrA
quinolone
- only used clinically as combination therapy
- RNA polymerase inhibitor
- only antibiotic in clinical use for blocking transcription
rifamycins
what mechanism of action can bind the beta subunit of bacterial RNA polymerase at an allosteric site, preventing chain elongation
rifamycin
- blocks a step in folic acid metabolism (folate synthesis)
- usually used in combination to achieve complete inhibition
sulfadrugs
What role does tetrahydrofolate play in one carbon metabolism?
Donates or accepts carbon in:
- purine synthesis
- dTMP synthesis
- Amino acid metabolism
which of the two tetrahydrofolate drug targets is slow killing, targeting the conversion of GTP to dihyropteroate
sulfamethoxazole
which of the two tetrahydrofolate drug targets prevents recycling of THF to DHF, messing up the redox
Trimethoprim
Using sulfamethoxazole along with trimethoprim results in a — fold increase in efficiency
100
what type of enzymatic inhibition does sulfamethoxazole function through?
competitive inhibition
what type of enzymatic inhibition does trimethoprim function through?
competitive inhibition
List the four types of intrinsic antibiotic resistance
- cell wall impermeability
- efflux pumps
- inactivating enzymes
- alternative pathways
List the three types of acquired antibiotic resistance mechanisms
- Point mutations
- Gene duplication/other alterations
- Gene transfer (efflux pumps/inactivating enzymes)
Which type of mechanisms are inducible: intrinsic or acquired?
intrinsic; these bacteria are often antibiotic producers themselves
What is the theory for how intrinsic antibiotic resistance mechanisms came about?
with the ability to synthesize antibiotics, resistance genes co-evolved to prevent antibiotic producers from committing suicide
what genus/species produces most of the polyketide-based macrolide antibiotics
streptomycetes
what are the three strategies for self-resistance in macrolide producers
- target modification
- expression of macrolide transport proteins
- macrolide inactivation
how does target modification self-resistance work?
macrolides typically bind to the 23s rRNA, but these producers modify their 23s rRNA to prevent binding
how does expression of macrolide transport protein self-resistance work?
the ABC transporter proteins (powered by ATP hydrolysis) pumps out macrolides
how does macrolide inactivation self-resistance work?
at the end of the macrolide biosynthetic pathway, an enzyme modifies the molecule by adding a protective group (usually glucose)
OleB pumps out and OleR reactivates
Why are the intrinsic methods of resistance not observed as a major route of resistance for antimicrobials (synthetic antibacterials)?
Bacteria have not been exposed to synthetic antibiotics for 100s of years (time is a factor)
How can beta-lactams be inactivated and what are the two types of this enzyme that accomplish this (along with their differences)
- the b-lactam ring can be hydrolyzed (using beta-lactamases)
- serine beta-lactamases have an intermediate (Class A, C, and D)
- zinc beta-lactamases have no intermediate (Class B)
what type antibiotics (producers) covalently modify the hydroxyl and amino groups of antibiotics to prevent binding to the 16s rRNA
aminoglycosides
