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. 2003 Feb;47(2):665-9.
doi: 10.1128/AAC.47.2.665-669.2003.

AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis

Melissa A Visalli  1 , Ellen Murphy, Steven J Projan, Patricia A Bradford
Affiliations

AcrAB multidrug efflux pump is associated with reduced levels of susceptibility to tigecycline (GAR-936) in Proteus mirabilis

Melissa A Visalli et al. Antimicrob Agents Chemother. 2003 Feb.

Abstract

Tigecycline has good broad-spectrum activity against many gram-positive and gram-negative pathogens with the notable exception of the PROTEEAE: A study was performed to identify the mechanism responsible for the reduced susceptibility to tigecycline in Proteus mirabilis. Two independent transposon insertion mutants of P. mirabilis that had 16-fold-increased susceptibility to tigecycline were mapped to the acrB gene homolog of the Escherichia coli AcrRAB efflux system. Wild-type levels of decreased susceptibility to tigecycline were restored to the insertion mutants by complementation with a clone containing a PCR-derived fragment from the parental wild-type acrRAB efflux gene cluster. The AcrAB transport system appears to be associated with the intrinsic reduced susceptibility to tigecycline in P. mirabilis.

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Figures

FIG. 1.
FIG. 1.
Genomic Southern blot showing transposon insertion into the chromosomes of two independently isolated insertion mutants. Lane 1, chromosomal DNA from the wild-type parent (G151); lane 2, positive control plasmid DNA (pCLL2300); lanes 3 and 4, chromosomal DNA from each of the insertion mutants (GC 6899 and GC6900). The presence of transposon insertion was detected by probing with the kanamycin resistance gene present in the transposable element.
FIG. 2.
FIG. 2.
Linear arrangement of P. mirabilis acrAB gene cluster.
See this image and copyright information in PMC

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