Mutation at the “Exit Gate” of the Salmonella Gyrase A Subunit Suppresses a Defect in the Gyrase B Subunit

Abstract

ABSTRACT In Salmonella enterica serovar Typhimurium, an S431P substitution in the B subunit of gyrase (allele gyrB651 ) confers resistance to nalidixic acid and causes reduced DNA superhelicity and hypersensitivity to novobiocin. Selection for novobiocin resistance allowed isolation of a mutation in the gyrA gene (allele gyrA659 ), a T467S substitution, which partially suppresses the supercoiling defect of gyrB651 . Modeling analysis suggests that this mutation acts by destabilizing the GyrA bottom dimer interface. This is the first example of a gyrA mutation that compensates for a gyrB defect.