GyrA Interacts with MarR To Reduce Repression of themarRABOperon inEscherichia coli

Abstract

Bacterial two-hybrid studies of randomly cloned Escherichia coli DNA identified a physical interaction between GyrA, subunit A of gyrase, and MarR, a repressor of the marRAB operon. GyrA-His immobilized on Ni-nitrilotriacetic acid (NiNTA) resin bound MarR, while MarR alone did not bind. GyrA interfered with MarR binding to marO, as detected by electrophoretic mobility assays. In a strain bearing the marRAB operon and a marO-lacZ reporter, overexpression of GyrA increased LacZ activity, indicating decreased repression of marO-lacZ by MarR. These results were confirmed by an increased survival of cells treated with quinolones and other antibiotics when GyrA was overexpressed. This work, like a previous study examining TktA (12), shows that unrelated proteins can regulate MarR activity. The findings reveal an unexpected regulatory function of GyrA in antibiotic resistance.

Aromatic Acid Metabolites of Escherichia coli K-12 Can Induce the marRAB Operon

“…In the case of MarR, numerous chemical compounds, such as benzoate, salicylate, 2,4-dinitrophenol, menadione, and plumbagin, have been shown to modulate its activity both in vivo and in vitro (1,3,9,19,22). Additionally, MarR activity is affected through proteinprotein interactions with enzymes such as transketolase A and DNA gyrase subunit A (11)(12).…”