SALICYLATE INDUCTION OF ANTIBIOTIC-RESISTANCE IN ESCHERICHIA-COLI - ACTIVATION OF THE MAR OPERON AND A MAR-INDEPENDENT PATHWAY

Since the growth of wild-type Escherichia coli in salicylate results i n a multiple antibiotic resistance phenotype similar to that of consti tutive mutants (Mar) of the chromosomal mar locus, the effect of salic ylate on the expression of the marRAB operon was investigated. The amo unt of RNA hybridizing with a mar-specific DNA probe was 5 to 10 times higher in wild-type cells grown with sodium salicylate (5.0 mM) than in untreated controls. Untreated Mar mutants had three to five times m ore mar-specific RNA than wild-type cells did. When a Mar mutant was t reated with salicylate, a 30- to 50-fold increase of mar-specific RNA was seen. In wild-type cells bearing a mar promoter-lacZ fusion on the chromosome, salicylate increased beta-galactosidase activity by sixfo ld. Thus, salicylate induces transcription of the marRAB operon. Other inducers of phenotypic multiple antibiotic resistance, e.g., benzoate , salicyl alcohol, and acetaminophen, but not acetate, also increased transcription from the mar promoter but to a lesser extent than did sa licylate. Both in wild-type and mar-deficient strains, growth in salic ylate resulted in increased antibiotic resistance, decreased permeatio n of the outer membrane to cephaloridine, increased micF transcription , and decreased amounts of OmpF. However, the magnitude of these chang es was generally greater in wild-type (mar-containing) cells. Thus, sa licylate and other compounds can induce transcription of the mar opero n and, presumably, give rise to multiple antibiotic resistance via thi s pathway. However, salicylate can also activate an unidentified, mar- independent pathway(s) which engenders multiple antibiotic resistance.