Rr. Ariza et al., REPRESSOR MUTATIONS IN THE MARRAB OPERON THAT ACTIVATE OXIDATIVE STRESS GENES AND MULTIPLE ANTIBIOTIC-RESISTANCE IN ESCHERICHIA-COLI, Journal of bacteriology, 176(1), 1994, pp. 143-148
Resistance to multiple antibiotics and certain oxidative stress compou
nds was conferred by three independently selected mutations (marR1, so
Q1, and cfxB1) that mapped to 34 min on the Escherichia coli chromosom
e. Mutations at this locus can activate the marRAB operon, in which ma
rR encodes a putative repressor of mar transcription and marA encodes
a putative transcriptional activator of defense genes against antibiot
ics and oxidants. Overexpression of the wild-type MarR protein reverse
d the phenotypes (antibiotic resistance and increased antioxidant enzy
me synthesis) of all three mutants. DNA sequence analysis showed that,
like marR1, the other two mutations were alterations of marR: a 285-b
p deletion in cfxB1 and a GC-->AT transition at codon 70 (Ala-->Thr) i
n soxQ1. All three mutations cause increased amounts of mar-specific R
NA, which supports the hypothesis that MarR has a repressor function i
n the expression of the marRAB operon. The level of mar RNA was furthe
r induced by tetracycline in both the marR1 and soxQ1 strains but not
in the cfxB1 deletion mutant. In the cfxB1 strain, the level of expres
sion of a truncated RNA, with or without tetracycline exposure, was th
e same as the fully induced level in the other two mutants. Overproduc
tion of MarR in the cfxB1 strain repressed the transcription of the tr
uncated RNA and restored transcriptional inducibility by tetracycline.
Thus, induction of the marRAB operon results from the relief of the r
epression exerted by MarR. The marRAB operon evidently activates both
antibiotic resistance and oxidative stress genes.