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Bacterial DNA Topoisomerase Inhibition Module

Module bacterial_dna_topoisomerase_inhibition 2 disorders Pathograph 2
A conserved antibacterial drug-mechanism module representing the bacterial type II topoisomerases — DNA gyrase (GyrA/GyrB) and topoisomerase IV (ParC/ParE) — that manage chromosomal supercoiling and decatenation during replication. Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) are the major drug class acting here: they trap the enzyme-DNA cleavage complex, converting the topoisomerase into a DNA-damaging agent that generates double-strand breaks and is bactericidal. Because gyrase and topoisomerase IV are bacterial enzymes distinct from human topoisomerases, fluoroquinolones are selectively toxic. This module defines the mechanism-of-action design pattern for fluoroquinolone treatments: conforming entries link a treatment to the gyrase/ topoisomerase target via target_mechanisms. It also encodes the quinolone-resistance-determining-region (QRDR) mutation and efflux resistance that gate fluoroquinolone use.
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Pathophysiology Nodes

2
2 shared nodes are defined in this module.
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Cell Types

0
No cell types are annotated for this module.
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Biological Processes

2
DNA Topological Change GO:0006265 Response to Antibiotic GO:0046677
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Notes

Antibacterial drug-mechanism module, not a specific disease. Disorder entries reference nodes via conforms_to (e.g., "bacterial_dna_topoisomerase_inhibition#DNA Gyrase and Topoisomerase IV (Fluoroquinolone Target)"), and their fluoroquinolone treatments point at that node via target_mechanisms. Key conformance / treatment target: "DNA Gyrase and Topoisomerase IV (Fluoroquinolone Target)". Nodes are druggable steps, not individual drugs.
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Used By Disorder Entries

2
Legionnaires Disease via DNA Gyrase and Topoisomerase IV Inhibition by Fluoroquinolones → DNA Gyrase and Topoisomerase IV (Fluoroquinolone Target)
Traveler's Diarrhea via Enteropathogen DNA Gyrase / Topoisomerase IV (Fluoroquinolone Target) → DNA Gyrase and Topoisomerase IV (Fluoroquinolone Target)
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Pathograph

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Pathograph: causal mechanism network for Bacterial DNA Topoisomerase Inhibition Module Interactive directed graph showing how this shared module's pathophysiology nodes connect.
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Pathophysiology

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DNA Gyrase and Topoisomerase IV (Fluoroquinolone Target)
therapeutic vulnerability
Bacterial DNA gyrase and topoisomerase IV break, pass, and reseal duplex DNA to manage supercoiling and decatenate replicated chromosomes. Fluoroquinolones bind the enzyme-DNA complex via a water-metal-ion bridge, block strand-passage catalysis, and stabilize the cleavage complex; release of the broken DNA underlies their bactericidal activity. Quinolones are the only current class that directly inhibits bacterial DNA synthesis, and their bacterial type II topoisomerase targets are distinct from human topoisomerases, giving selectivity.
DNA Topological Change GO:0006265
Used by disorders
Legionnaires Disease as DNA Gyrase and Topoisomerase IV Inhibition by Fluoroquinolones
Traveler's Diarrhea as Enteropathogen DNA Gyrase / Topoisomerase IV (Fluoroquinolone Target)
Downstream
  • Fluoroquinolone Target Resistance QRDR mutations and efflux protect the topoisomerase target, escaping fluoroquinolone action.
Fluoroquinolone Target Resistance
adaptive escape
Resistance to fluoroquinolones arises predominantly from mutations in the quinolone-resistance-determining region (QRDR) of the GyrA and ParC subunits that lower drug-target affinity, from increased efflux-pump expression, and from acquired plasmid-mediated quinolone-resistance genes. High-level resistance is common in some pathogens (e.g. typhoidal Salmonella), which is why fluoroquinolones must be susceptibility-guided rather than assumed effective.
Response to Antibiotic GO:0046677