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Lophirones B and C induce oxidative cellular death pathway in Acinetobacter baumannii by inhibiting DNA gyrase

T O Ajiboye1, N O Aliyu1, R A Ajala-Lawal1

  • 1Antioxidants, Redox Biology and Toxicology Research Group, Department of Medical Biochemistry, College of Health Sciences, Nile University of Nigeria, FCT-Abuja, Nigeria.

Microbial Pathogenesis
|March 16, 2019
PubMed

Insights

DNA gyrase inactivation increases Acinetobacter baumannii sensitivity to lophirones B and C by affecting oxidative stress and iron levels. This highlights DNA gyrase

Area of Science:

  • Microbiology
  • Antimicrobial Resistance
  • Oxidative Stress

Background:

  • Acinetobacter baumannii is a significant opportunistic pathogen.
  • Understanding mechanisms of antimicrobial action is crucial for developing new treatments.
  • Lophirones B and C are natural compounds with potential antimicrobial activity.

Purpose of the Study:

  • To investigate the role of DNA gyrase in the oxidative stress response and sensitivity of A. baumannii to lophirones B and C.
  • To elucidate the mechanisms underlying the antimicrobial activity of lophirones B and C.

Main Methods:

  • Minimum inhibitory concentration (MIC) and time-kill assays were used to determine bacterial sensitivity.
  • Mutant strains with inactivated sodB, katG, recA, and gyrA genes were employed.
  • Superoxide anion radical and hydrogen peroxide accumulation were measured.
  • Intracellular Fe2+ content and NAD+/NADH ratio were analyzed.

Main Results:

  • Inactivation of sodB, katG, and recA enhanced A. baumannii sensitivity to lophirones B and C.
  • These inactivations also increased reactive oxygen species (ROS) accumulation, which was reversed by thiourea.
  • GyrA inactivation inhibited lophirone-mediated ROS accumulation.
  • Lophirones B and C increased Fe2+ levels, and dipyridyl reversed sensitivity.
  • Lophirones B and C reduced the NAD+/NADH ratio.

Conclusions:

  • DNA gyrase plays a critical role in mediating the accumulation of ROS, Fe2+ release, and cell death induced by lophirones B and C in A. baumannii.
  • Targeting DNA gyrase could be a strategy to enhance the efficacy of lophirones against A. baumannii infections.
Keywords:
Acinetobacter baumanniiDNA gyrase AFenton chemistryHydroxyl radicalLophirones B and COxidative DNA damage

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