Drug Information

Drug (ID: DG00487) and It's Reported Resistant Information

• Name: Fluoroquinolones
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (4 diseases)
  Bacterial infection [ICD-11: 1A00-1C4Z]; [1]
  Campylobacteriosis [ICD-11: 1C40]; [2]
  COVID-19 [ICD-11: 1D92]; [3]
  Helicobacter pylori infection [ICD-11: DA60]; [4]
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (1 diseases)
  Tuberculosis [ICD-11: 1B10]; [5]

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Bacterial infection [ICD-11: 1A00-1C4Z]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Fluoroquinolone efflux MFS transporter QepA1 (QEPA1) [6]

• Resistant Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli C316; 562
• Experiment for Molecule Alteration: DNA sequencing and alignment assay
• Experiment for Drug Resistance: Agar dilution method assay
• Mechanism Description: QepA is a new quinolone efflux pump protein responsible for fluoroquinolone resistance.

Key Molecule: Multidrug resistance protein PmpM (PMPM) [1]

• Resistant Disease: Pseudomonas aeruginosa infection [ICD-11: 1A00-1C4Z]
• Molecule Alteration: Expression; Inherence
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Escherichia coli kAM32/pSTV28; 562
• Experiment for Molecule Alteration: PCR amplification and DNA sequence assay
• Experiment for Drug Resistance: MIC assay
• Mechanism Description: PmpM is a multi drug efflux pump coupled with hydrogen ions, which reduces the intracellular drug concentration and produces drug resistance.

Tuberculosis [ICD-11: 1B10]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: DNA gyrase subunit B (GYRB) [5]

• Resistant Disease: Tuberculosis [ICD-11: 1B10.0]
• Molecule Alteration: Mutation; R658G
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: GeneSeq assay; Bioinformatics assay
• Mechanism Description: Out of total 112 mycobacterial positive cultures, five?M. bovis?were isolated and underwent WGS. All sequenced strains belonged to?Mycobacterium tuberculosis var bovis, spoligotype BOV_1; BOV_11. Resistance gene mutations were determined in 100% of strains to pyrazinamide (pncA?and?rpsA), isoniazid (KatG?and?ahpC), ethambutol (embB,?embC,?embR?and?ubiA), streptomycin (rpsl) and fluoroquinolones (gyrA?and?gyrB). Rifampin (rpoB?and?rpoC) and delamanid (fbiC) resistance genes were found in 80% of strains. The major represented virulence classes were the secretion system, cell surface components and regulation system.

References

• Ref 1: An H(+)-coupled multidrug efflux pump, PmpM, a member of the MATE family of transporters, from Pseudomonas aeruginosa. J Bacteriol. 2004 Jan;186(1):262-5. doi: 10.1128/JB.186.1.262-265.2004.
• Ref 2: [Overview of resistance mechanisms in Campylobacter]Zhonghua Yu Fang Yi Xue Za Zhi. 2018 Oct 6;52(10):1072-1077. doi: 10.3760/cma.j.issn.0253-9624.2018.10.021.
• Ref 3: Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 Nature. 2021 May;593(7857):130-135. doi: 10.1038/s41586-021-03398-2. Epub 2021 Mar 8.
• Ref 4: Helicobacter pylori infection and antibiotic resistance - from biology to clinical implicationsNat Rev Gastroenterol Hepatol. 2021 Sep;18(9):613-629. doi: 10.1038/s41575-021-00449-x. Epub 2021 May 17.
• Ref 5: Genetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing. BMC Genomics. 2024 Nov 1;25(1):1024.
• Ref 6: New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob Agents Chemother. 2007 Sep;51(9):3354-60. doi: 10.1128/AAC.00339-07. Epub 2007 Jun 4.