Antibacterial Activity of DC-159a Against Salmonella Typhimurium

Microb Drug Resist. 2019 Jan/Feb;25(1):14-22. doi: 10.1089/mdr.2018.0078. Epub 2018 Jul 23.

Abstract

Quinolones show excellent antibacterial activity against Salmonella isolates. Recently, however, quinolone resistance has been increasing in bacteria. This study aimed to examine in vitro, and compare the activity of DC-159a against Salmonella enterica serovar Typhimurium with that of ciprofloxacin and nalidixic acid. Inhibitory effects of quinolones were assessed by the drug concentration needed to inhibit the supercoiling activity of recombinant DNA gyrases by 50% (IC50). Dilution methods were used to determine the minimum inhibitory concentration (MIC) of quinolones against two different strains, Salmonella Typhimurium and Salmonella Enteritidis. The IC50s of DC-159a against mutant DNA gyrases were much lower than those of nalidixic acid and ciprofloxacin. In particular, the IC50 of DC-159a against DNA gyrase with double mutation was less than 1/50 that of ciprofloxacin and nalidixic acid. MICs of DC-159a were higher than those of ciprofloxacin but lower than those of nalidixic acid. However, the estimated MICs of DC-159a against Salmonella strains with mutant DNA gyrase were lower than those of ciprofloxacin and nalidixic acid. Therefore, DC-159a can be suggested as an antibiotic candidate for treating salmonellosis caused by quinolone-resistant S. Typhimurium.

Keywords: Typhimurium; antimicrobial resistance; fluoroquinolone; nontyphoidal.

MeSH terms

  • Aminopyridines / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • Ciprofloxacin / pharmacology
  • DNA Gyrase / genetics
  • Fluoroquinolones / pharmacology*
  • Humans
  • Microbial Sensitivity Tests / methods
  • Mutation / genetics
  • Nalidixic Acid / pharmacology
  • Quinolones / pharmacology
  • Salmonella Infections / drug therapy
  • Salmonella Infections / microbiology
  • Salmonella enterica / drug effects*
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / genetics

Substances

  • 7-(7-amino-7-methyl-5-azaspiro(2.4)heptan-5-yl)-6-fluoro-1-(2-fluoro-1-cyclopropyl)-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid
  • Aminopyridines
  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Quinolones
  • Nalidixic Acid
  • Ciprofloxacin
  • DNA Gyrase