Interaction of the MexA and MexB components of the MexAB-OprM multidrug efflux system of Pseudomonas aeruginosa: identification of MexA extragenic suppressors of a T578I mutation in MexB.

A T578I mutation in MexB compromised the protein's contribution to antimicrobial resistance and negatively impacted its interaction with MexA. Mutations causing single amino acid changes in the C-terminal domain of MexA (R221H, L245F, E254K, and V259I) suppressed the antimicrobial susceptibility of a MexB(T578I)-expressing Pseudomonas aeruginosa strain and restored a MexA interaction with MexB(T578I). These data confirm the importance of the MexA C-terminal region in MexB binding and the likely significance of the region surrounding T587I of MexB in MexA interaction.