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

INSERM U431, Faculté de Médecine, Avenue J. F. Kennedy, 30908 Nîmes cedex 02, France,¹ Centre de Biochimie Structurale, INSERM U554-CNRS UMR5048, Université Montpellier I, 15 Av. Charles Flahault, 34060 Montpellier cedex, France,² Centre de Génétique Moléculaire, CNRS, 91198 Gif-sur-Yvette cedex, France³

Received 7 July 2005/ Accepted 12 July 2005

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.

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