Cross-resistance to nalidixic acid, trimethoprim, and chloramphenicol associated with alterations in outer membrane proteins of Klebsiella, Enterobacter, and Serratia.

We studied in vitro mutants of Klebsiella, Enterobacter, and Serratia cross-resistant to nalidixic acid, trimethoprim, and chloramphenicol that were similar to mutants found in vivo. The sole mechanism for this type of resistance appeared to be a reduction in permeability of the cell envelope. The mutants had significantly lower rates of uptake of glucose and chloramphenicol, but binding of chloramphenicol to ribosomes was normal. In addition, the amounts of dihydrofolate reductase were similar in both wild-type and cross-resistant mutants of Klebsiella. Examination of the bacterial outer membrane revealed that the amount of at least one major protein, with a molecular size of approximately 40 kilodaltons, was decreased in the mutants. Therefore the resistance seemed likely to be due to the reduction in quantity of these outer membrane proteins, possibly porins, in the mutant bacteria.