Contribution of outer membrane efflux protein OprM to antibiotic resistance in Pseudomonas aeruginosa independent of MexAB.
A Pseudomonas aeruginosa strain carrying an insertion of an omega Hg interposon in the mexB gene (mexB::omega Hg; strain K879) produced markedly reduced but still detectable levels of OprM, the product of the third gene of the mexAB-oprM multidrug efflux operon. By using a lacZ transcriptional fusion vector, promoter activity likely responsible for OprM expression in the mexB::omega Hg mutant was identified upstream of oprM. Introduction of the oprM gene, but not the mexAB genes, into a P. aeruginosa multidrug-susceptible delta mexAB-oprM mutant increased resistance to quinolones, cephalosporins, erythromycin, and tetracycline. A delta mexAB-oprM strain carrying the oprM gene accumulated markedly less antibiotic than the deletion strain without oprM. Antibiotic accumulation by the MexAB- OprM+ strain was markedly enhanced upon treatment of cells with the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), indicating that MexAB-independent OprM function likely involves an efflux process. Moreover, pretreatment of cells with CCCP prior to the accumulation assay abrogated any differences in accumulation levels between the MexAB- OprM+ and MexAB- OprM- strains, indicating that reduced drug accumulation by the OprM+ strain (in the absence of CCCP) cannot be due to OprM-mediated reduction in outer membrane permeability. It appears, therefore, the OprM can be expressed and function in a drug efflux capacity independent of MexAB.
Zhao
Q
Q
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Li
X Z
XZ
Srikumar
R
R
Poole
K
K
D001425:Bacterial Outer Membrane Proteins / Q000502:physiology*; D001426:Bacterial Proteins / Q000502:physiology*; D001692:Biological Transport; D004352:Drug Resistance, Microbial / Q000502:physiology*; D018432:Drug Resistance, Multiple / Q000502:physiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000502:physiology*
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins