Open AccessAminoglycoside-inducible expression of the mexAB-oprM multidrug efflux operon in Pseudomonas aeruginosa: Involvement of the envelope stress-responsive AmgRS two-component system
Author(s) -
Michael Fruci,
Keith Poole
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0205036
Subject(s) - efflux , operon , aminoglycoside , pseudomonas aeruginosa , microbiology and biotechnology , biology , atp binding cassette transporter , chemistry , biochemistry , transporter , genetics , gene , antibiotics , bacteria , escherichia coli
Exposure of P . aeruginosa to the aminoglycoside (AG) paromomycin (PAR) induced expression of the PA3720- armR locus and the mexAB-oprM multidrug efflux operon that AmgR controls, although PAR induction of mexAB-oprM was independent of armR . Multiple AGs promoted mexAB-oprM expression and this was lost in the absence of the amgRS locus encoding an aminoglycoside-activated envelope stress-responsive 2-component system (TCS). Purified AmgR bound to the mexAB-oprM promoter region consistent with this response regulator directly regulating expression of the efflux operon. The thiol-active reagent, diamide, which, like AGs, promotes protein aggregation and cytoplasmic membrane damage also promoted AmgRS-dependent mexAB-oprM expression, a clear indication that the MexAB-OprM efflux system is recruited in response to membrane perturbation and/or circumstances that lead to this. Despite the AG and diamide induction of mexAB-oprM , however, MexAB-OprM does not appear to contribute to resistance to these agents.