Impact of zinc uptake regulator Zur on the susceptibility and oxidative stress response of Acinetobacter baumannii to antibiotics

Abstract

Zinc is a highly coveted redox-inactive micronutrient required for the growth and virulence of Acinetobacter baumannii. In this study, the role of the zinc uptake regulator Zur in the susceptibility and oxidative stress response of A. baumannii to antibiotics was evaluated. Inactivation of zur increased the susceptibility of A. baumannii AB5075 to colistin, gentamicin, rifampicin and tigecycline. Furthermore, activities of superoxide dismutase and catalase decreased significantly in the Δzur mutant compared with the parental strain. Colistin, gentamicin, rifampicin and tigecycline raised the superoxide anion radical (·O2-) and hydrogen peroxide (H2O2) contents of the Δzur mutant compared with the parental strain. In addition, the antibiotics lowered glutathione and concomitantly raised glutathione disulphide levels in the Δzur mutant. All of the antibiotics, except tigecycline, significantly raised the NAD+/NADH and ADP/ATP ratios in A. baumannii. We conclude that decreased capability of the Δzur mutant to detoxify reactive oxygen species increased its susceptibility to antibiotics.