An unusual interaction between the target of nalidixic acid and novobiocin

Abstract

BACTERIAL mutation resulting in drug resistance often has pleiotropic effects. Amongst these are alterations in susceptibilities to other drugs. Perhaps the best understood and studied of these interactions are antibiotic resistance mutations that involve genes of ribosomal proteins. The pleiotropic effects induced by ribosomal mutations are usually interpreted by interaction of different ribosomal proteins in the ribosomal organelle. For example, it has been observed that certain ribosomal mutations to neomycin-kanamycin (nek) resistance in Escherichia coli mask the phenotype of spectinomycin (spc) resistance¹. Similarly, there is also interaction between ribosomal ambiguity (ram) and the streptomycin (str) genes². More recently, it has been observed that there is an interaction of ribosomal (str) and RNA polymerase subunit (rif) mutations³. I describe here an interaction between mutations involving resistance against two quite different drugs, nalidixic acid and novobiocin, both of which affect DNA replication. This genetic interaction may reflect existence of a protein complex in the DNA replication machinery which has already been postulated on other grounds (see ref. 4).