Drug Information

Drug (ID: DG00561) and It's Reported Resistant Information

• Name: 3'-(AM)P-quinolone {1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-7-[(3S)-3-(aminomethyl)-1-pyrrolidinyl]-4-oxo-3-quinolinecarboxylic acid}
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Anthrax [ICD-11: 1B97]; [1]
• Target: .; NOUNIPROTAC; [1]

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Anthrax [ICD-11: 1B97]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: DNA gyrase subunit A (GYRA) [1]

• Molecule Alteration: Mutation; p.S85+p.S85F+p.E89K+p.E89A
• Resistant Disease: Anthrax [ICD-11: 1B97.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Escherichia coli strain; 562
• In Vitro Model: Bacillus anthracis strain; 1392
• Experiment for Molecule Alteration: DNA cleavage assay
• Mechanism Description: The most common gyrase mutations in quinolone-resistant strains of B. anthracis are found at the conserved serine and glutamic acid residues (GyrAS85 and GyrAE89). In laboratory strains selected for resistance against ciprofloxacin and/or moxifloxacin (two widely prescribed quinolone antibacterials), approximately 80% of the isolates carried a GyrAS85L mutation (either alone or in combination with other gyrase/topoisomerase IV amino acid changes). The only other mutation reported to cause resistance without any other gyrase/topoisomerase IV changes was a GyrAE89K substitution.

References

• Ref 1: Interactions between Quinolones and Bacillus anthracis Gyrase and the Basis of Drug Resistance .Biochemistry. 2017 Aug 15;56(32):4191-4200. doi: 10.1021/acs.biochem.7b00203. Epub 2017 Aug 1. 10.1021/acs.biochem.7b00203