marA, a regulated locus which controls expression of chromosomal multiple antibiotic resistance in Escherichia coli

Abstract

Stable chromosomal multiple-antibiotic-resistant (Mar) mutants of Escherichia coli, derived by exposing susceptible cells to low concentrations of tetracycline or chloramphenicol, express cross-resistance to structurally unrelated antibiotics. The entire resistance phenotype is reversed to susceptibility by insertion of transposon Tn5 into a locus, designated marA, near 34 min on the chromosome (A. M. George and S. B. Levy, J. Bacteriol. 155:541-548, 1983). Strains in which 39 kbp of chromosomal DNA, including marA, had been deleted were unable to produce Mar mutants. The deletion strain could be complemented in trans by introduction of intact marA+ on plasmid F'506. Junction fragments from a strain containing marA::Tn5 were cloned, exploiting kanamycin resistance on Tn5 for selection. They were used as probes to search a phasmid library of E. coli K-12 for recombinants containing the marA+ region. Two phasmids which contained regions hybridizing to this probe were identified and shown to complement delta marA in a deletion strain. From one phasmid, several marA-containing fragments were cloned: those of greater than or equal to 7.8 kbp restored the ability to form Mar mutants in a deletion strain. These Mar mutants were shown to be dependent on the cloned marA fragment. Chromosomal as well as recombinant Mar mutants showed increased expression of a marA-specific mRNA species of about 1.4 kb, which was barely or not detectable in wild-type strains. Exposure of mutants and, to a lesser extent, parental strains to tetracycline or chloramphenicol resulted in elevated levels of mRNA which hybridized to the marA probe. These results indicate that the marA locus is needed for production of Mar mutants and is regulated, responding to at least two antibiotics to which it controls resistance.

Identification and analysis of aarP, a transcriptional activator of the 2'-N-acetyltransferase in Providencia stuartii

“…It has been demonstrated that the accumulation of marA mRNA is increased by exposure of cells to either tetracycline, chloramphenicol, or salicylate (8,9,20). To determine if aarP mRNA accumulation was also increased by these agents, the accumulation of aarP mRNA was examined by Northern blot analysis after treating cells for 1.5 h with either chloramphenicol (2 g/ml), tetracycline (50 g/ml), or salicylate (5 mM).…”

Dual regulation of inaA by the multiple antibiotic resistance (mar) and superoxide (soxRS) stress response systems of Escherichia coli

“…The fact that the mar pathway is inducible by certain aromatic weak acids (7) and antibiotics (2,15) at relatively lower temperatures may mean that mar is primarily an adaptation to free-living situations. In contrast, the soxRS pathway has recently been shown to be stimulated by the biological signal molecule nitric oxide and to confer resistance to mouse macrophages (27).…”

Repressor mutations in the marRAB operon that activate oxidative stress genes and multiple antibiotic resistance in Escherichia coli

“…Previous work has shown that, independently of soxRS, the soxQl and cfxBl mutations cause transcriptional activation of some of the soxRS regulon genes and the induction of seven other proteins not influenced by soxRS or elevated by oxidative stress (14). Both soxQl and cfxBl, together with the previously identified marRi, map to the 34-min locus on the E. coli chromosome (6,13,14,19), which has been implicated in chromosome-mediated multiple antibiotic resistance (mar) (6,13,16). The soxQl-and the cfxBl-dependent phenotypes do not depend on the soxRS locus, and gene induction by soxRS in response to redox stress does not depend on mar (14).…”