Loss of OmpC Porin in a Strain of Salmonella typhimurium Causes Increased Resistance to Cephalosporins During Therapy

Abstract

Nimal inhibitory concentrations of cephalosporins for a strain of Salmonella typhimurium from one patient increased severalfold after starting therapy with cephalexin. The first isolate with increased resistance (S20323)and an earlier, less resistant isolate (SI7069) each had a TEM-1 β-lactamase with similar Vmax and Km values. Intact cells of S20323 grown in a high osmolality medium hydrolyzed cephalosporin substrates much more slowly than did intact cells of Sl7069 at low substrate concentrations, a result indicating slower diffusion of cephalosporins into S20323. In low osmolality media, Sl7069 produced both OmpF and OrnnC porins; S20323 produced only OmpF porin. In high osmolality media with osmotic activity similar to that in the patient's tissues, synthesis of the OmpF porin was repressed in both strains and left S20323 with undetectably low levels of any porin. The increased β-lactam resistance in S20323 is apparently a consequence of the loss of the OmpC porin.