Molecular genetics of polymyxin resistance in Salmonella typhimurium.

Resistance to Polymyxin and CAP are conferred by a point mutation, pmrA505, in position 81 that results in an Arg to His substitution in pmrA, a regulator protein. The protein, pmrB is expressed in the cell membrane. This is consistent with the hypothesis that it is a sensor/kinase protein. A newly discovered gene, pmrD, confers resistance to polymyxin B equal to that of pmrA505 when expressed on a multicopy plasmid, but such transformed strains are not resistant to CAP. Evidence is presented that pmrA505 can be expressed, but only suboptimally, in the absence of pmrD. However, there is an absolute requirement for pmrA+ in order for pmrD to express resistance to polymyxin B. It is therefore suggested that pmrD is regulated by the two component regulatory pair pmrAB.