Antibiotics acting in cytoplasm

What antibiotics target folate? How do they work?

Sulphonamides and trimethoprim

Bacteria able to synthesise own folic acid

Sulphonamides: structural analogue of regular substrate PABA

Trimethoprim: inhibits dihydrofolate reductase (later stage of synthesis)

Often given together as work synergistically

Antibiotic classes targeting DNA architecture and chromosome replication

Quinolones

Nitroimidazoles

Nitrofurans

Basic fluoroquinolone overview

Synthetic

All come from nalidixic acid

Broad spec, good bioavailability

Frequent resistance

Target DNA gyrase and topoisomerase IV

Mechanism of action of fluoroquinolones

Gyrase cuts DNA

Fluoroquinolone binds gyrase-DNA complex

Fluoroquinolone prevents re-ligation of DNA

Get double strand break of chromosome

Examples of fluoroquinolones

2nd gen: Ciprofloxacin

3rd gen: Moxifloxacin (serious side effects so restricted use)

Enrofloxacin

Overview of Metronidazole

Nitronidazole

Nitro group reduced by bacterial enzyme

Produces cytotoxic free radicals that damage DNA

Only work anaerobically

Overview of Nitrofuarantoin

Nitrofuran

Only works when highly concentrated in urine: only for UTIs

Get reactive intermediates produced

Antibiotic inhibiting transcription

Rifampicin

Used for TB treatment

How does rifampicin work?

Binds to bacterial RNA polymerase

Prevents transition from initiation to elongation during transcription

Antibiotics inhibiting protein synthesis

Aminoglycosides

Tetracyclines

Macrolides

Chloramphenicol

Lincosamides

Oxazolidinones

Streptogramins

Aminoglycoside overview

Bactericidal

Bind 16s rRNA om 30S ribosome subunit

Used for serious G- infections

Aerobes only

Nephrotoxic and ototoxic

Amikacin, gentamicin, streptomycin

Spectinomycin overview

Similar to aminoglycosides but doesn’t cause misreading of mRNA

Bacteriostatic

Blocks mRNA interaction with 30S ribosome

Mostly for penicillin resistant N. gonorrhoeae

Tetracycline overview

Bacteriostatic

Broad-spectrum

Binds 30S subunit, directly blocks binding of aa-tRNA to ribosomal A-site

Reduced absorption if given with food

Chloramphenicol overview

Bacteriostatic

Broad spectrum but very toxic

Binds 23S rRNA in 50S subunit, interfering with peptidyl transferase

Use for meningitis, also topically for corneal ulcers

Pleuromutilin overview

Peptide transferase on 50S ribosome subunit

CAP

S. aureus

Macrolide overview

Binds 50S ribosomal subunit preventing peptide chain elongation

G+ and atypical pneumonia

Azithromycin, Erythromycin, Clarithromycin

Lincosamides overview

Binds 50S subunit blocking ribosome exit tunnel

Anaerobic infections, skin infections

Clindamycin similar but better spectrum

Overview of fusidic acid

Binds EF-G on ribosome, inhibiting release of EF-GDP blocking further elongation

Topical use against Staph

Mupirocin mech of action

Inhibition of isoleucine-tRNA synthetase

Potential novel targets for inhibiting protein synthesis

Initiation factors

Elongation factors

Termination factors

Etc