A novel GntR-ABC efflux system mediates oxidative stress response, drug resistance, motility and virulence in Acinetobacter baumannii ATCC 17978

INTRODUCTION: Acinetobacter baumannii is a highly adaptable opportunistic pathogen, notorious for its persistence in healthcare environments and its remarkable ability to withstand oxidative stress, antimicrobial treatments, and immune defenses.

METHODS: In this study, we characterized the role of the GntR family transcriptional regulator AUO97_RS16340 and its associated ABC efflux pump (AUO97_RS16355-RS16360-RS16365), previously identified as part of the OxyR regulon.

RESULTS: Through gain- and loss-of-function analyses, we demonstrate that this GntR regulator positively regulates the expression of the adjacent ABC efflux pump and plays a critical role in tolerance to H2O2-induced oxidative damage. Furthermore, we show that this efflux system contributes to multiple virulence-associated traits, including antimicrobial resistance, surface-associated motility, and virulence.

DISCUSSION: Our findings reveal a new efflux system that links oxidative stress adaptation, efflux-mediated antimicrobial susceptibility, and pathogenicity in A. baumannii strain ATCC 17978. Given the high conservation of the GntR transcriptional regulator and its associated efflux pump across A. baumannii genomes, these components represent promising therapeutic targets. Disrupting their activity could sensitize bacteria to oxidative stress and antimicrobials while attenuating virulence, providing a potential strategy to combat multidrug-resistant A. baumannii.