Contributions of ferric uptake regulator Fur to the sensitivity and oxidative response of Acinetobacter baumannii to antibiotics

Abstract

Ferric uptake regulator (Fur) is important in the regulation of bacterial iron metabolism and uptake of Fe from the environment. We evaluated the contribution of fur to the sensitivity and oxidative response of A. baumannii to antibiotics. Deletion of fur increased the sensitivity of A. baumannii AB5075 to colistin, gentamicin, rifampicin and tigecycline. Furthermore, activities of superoxide dismutase and catalase in Δfur mutant decreased significantly compared to the parental strain. Conversely, •O₂- and H₂O₂ accumulate in colistin, gentamicin, rifampicin or tigecycline-treated Δfur mutant compared to the parental strain. Ferrous ion (Fe²⁺) content of Δfur mutant increased compared to the parental strain. Fe chelator 2,2'-bipyridyl lowered the sensitivity of A. baumannii to the antibiotics. The antibiotics, except tigecycline, raised the NAD+/NADH and ADP/ATP ratio of Δfur mutant compared to the WT. Glutathione content of Δfur mutant was significantly depleted compared to parental strain following exposure to the antibiotics. We conclude that decreased capability of Δfur mutant to detoxify reactive oxygen species raised its susceptibility to antibiotics through Fenton chemistry.

Keywords: Acinetobacter baumannii; Ferric uptake regulator; Ferrous ion; Glutathione; Reactive oxygen species.