Aer is a bidirectional redox sensor mediating negative chemotaxis to antibiotic-induced ROS in Escherichia coli

ABSTRACT Bacterial swarms employ many mechanisms to reduce their exposure to antibiotics, including actively avoiding them. We show in this study that the avoidance response in Escherichia coli swarms is dependent on the chemoreceptor Aer, known to perform oxygen- or aero-taxis by sensing metabolic flux through the electron transport chain (ETC) via a flavin adenine dinucleotide (FAD) cofactor bound to its P er- A rnt- S im (PAS) domain. We find that Aer generates an FAD-dependent repellent or negative chemotaxis signal to the known reactive oxygen species (ROS) H₂O₂, thus sensing oxidative stress. Expression of the catalase–peroxidase enzyme KatG, which scavenges intracellular ROS, abrogates the repellent signal generated by both H₂O₂ and antibiotics. The ability of Aer to detect both oxidizing and reducing intracellular environments redefines its functional range and establishes Aer as a bidirectional redox sensor. Our study also provides independent behavioral evidence that certain antibiotics generate intracellular ROS, while offering a sensitive assay for detecting these reactive species. IMPORTANCE Motile bacteria rely on aerotaxis to seek environments that maximize energy production. We show that in Escherichia coli , Aer mediates not only positive chemotaxis toward favorable redox conditions but also negative chemotaxis in response to unfavorable ones, actively moving away from oxidizing environments, including reactive oxygen species (ROS)-generating antibiotics, a previously unrecognized behavioral mechanism for bacterial survival under oxidative stress. The ability of Aer to detect both oxidizing and reducing cellular environments reveals an unexpected sensory versatility, shared to varying degrees by other E. coli chemoreceptors.