Affiliation:
1. Center for Adaptation Genetics and Drug Resistance
2. Departments of Molecular Biology and Microbiology
3. of Medicine, Tufts University School of Medicine, Boston, Massachusetts 02111
Abstract
ABSTRACT
Thirteen spontaneous multiple-antibiotic-resistant (Mar) mutants of
Escherichia coli
AG100 were isolated on Luria-Bertani (LB) agar in the presence of tetracycline (4 μg/ml). The phenotype was linked to insertion sequence (IS) insertions in
marR
or
acrR
or unstable large tandem genomic amplifications which included
acrAB
and which were bordered by IS
3
or IS
5
sequences. Five different
lon
mutations, not related to the Mar phenotype, were also found in 12 of the 13 mutants. Under specific selective conditions, most drug-resistant mutants appearing late on the selective plates evolved from a subpopulation of AG100 with
lon
mutations. That the
lon
locus was involved in the evolution to low levels of multidrug resistance was supported by the following findings: (i) AG100 grown in LB broth had an important spontaneous subpopulation (about 3.7 × 10
−4
) of
lon
::IS
186
mutants, (ii) new
lon
mutants appeared during the selection on antibiotic-containing agar plates, (iii)
lon
mutants could slowly grow in the presence of low amounts (about 2× MIC of the wild type) of chloramphenicol or tetracycline, and (iv) a
lon
mutation conferred a mutator phenotype which increased IS transposition and genome rearrangements. The association between
lon
mutations and mutations causing the Mar phenotype was dependent on the medium (LB versus MacConkey medium) and the antibiotic used for the selection. A previously reported unstable amplifiable high-level resistance observed after the prolonged growth of Mar mutants in a low concentration of tetracycline or chloramphenicol can be explained by genomic amplification.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
45 articles.
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