Two distinct mechanisms grouped for clinical co-deployment. (1) DNA gyrase + topoisomerase IV — quinolones bind the enzyme-DNA complex → DNA strand breakage. (2) Bacterial folate synthesis — sulfonamides mimic PABA and competitively inhibit dihydropteroate synthase (DHPS, first step); trimethoprim inhibits dihydrofolate reductase (DHFR, downstream); the sulfonamide + trimethoprim combo (TMP-SMX) is sequential blockade → synergy. Metronidazole is activated by anaerobic ferredoxin/flavodoxin reduction → DNA-damaging nitro radicals; only anaerobes + microaerophilic protozoa can activate it. Nitrofurantoin is similarly activated by bacterial nitroreductases → multi-target damage (DNA, ribosome, metabolic enzymes); urinary concentration drives UTI activity despite low plasma levels.
Organ Systems
immune-hematologic
Pathway Steps
bacterial-dna-supercoiling → bacterial-dna-replication — via DNA gyrase + topoisomerase IV maintain negative supercoils + decatenate daughter chromosomes. Bacterial DNA gyrase and topoisomerase IV manage the supercoiling required for replication — enzymes humans lack in this form, giving selectivity. Fluoroquinolones (ciprofloxacin) trap these enzymes on DNA, causing lethal double-strand breaks: a key antibacterial target.
paba → tetrahydrofolate — via DHPS → DHF → DHFR → THF; sulfonamides block DHPS, trimethoprim blocks DHFR. Bacteria must synthesize folate de novo from PABA (they cannot import it as humans do), via dihydropteroate synthase and dihydrofolate reductase. Sulfonamides (PABA mimics) and trimethoprim block consecutive steps; their synergy (co-trimoxazole) exploits a pathway humans lack — the basis of selective toxicity.
Known Modulators
levofloxacin (inhibitor) — DNA gyrase + topoisomerase IV. respiratory fluoroquinolone; community pneumonia + complicated UTI; QT prolongation + tendinopathy + aortic-aneurysm signal + neuropsychiatric tail