Macrolide Antibiotic-Mediated Downregulation of MexAB-OprM Efflux Pump Expression in Pseudomonas aeruginosa

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Investigation of MexAB-OprM efflux pump gene expression in clinical isolates of pseudomonas aeruginosa isolated from Intensive Care Unit

Background and Aims: Pseudomonas aeruginosa is one of the most important pathogens of nosocomial infections, especially in the ICU (Intensive Care Unit), which has resistance to a wide range of antibiotics, especially Carbapenems. Among the most important resistance mechanisms of this bacteria against carbapenems are MexAB-OprM efflux pump. Therefore, the aim of this study was to evaluate the g...

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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 w...

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Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-oprM efflux pumps in Pseudomonas aeruginosa.

To find the exact substrate specificities of three species of tripartite efflux systems of Pseudomonas aeruginosa, MexAB-OprM, MexCD-OprJ, and MexXY-OprM, we constructed a series of isogenic mutants, each of which constitutively overproduced one of the three efflux systems and lacked the other two, and their isogenic mutants, which lacked all these systems. Comparison of the susceptibilities of...

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CpxR Activates MexAB-OprM Efflux Pump Expression and Enhances Antibiotic Resistance in Both Laboratory and Clinical nalB-Type Isolates of Pseudomonas aeruginosa

Resistance-Nodulation-Division (RND) efflux pumps are responsible for multidrug resistance in Pseudomonas aeruginosa. In this study, we demonstrate that CpxR, previously identified as a regulator of the cell envelope stress response in Escherichia coli, is directly involved in activation of expression of RND efflux pump MexAB-OprM in P. aeruginosa. A conserved CpxR binding site was identified u...

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siRNA-mediated gene silencing of MexB from the MexA-MexB-OprM efflux pump in Pseudomonas aeruginosa

To gain insights into the effect of MexB gene under the short interfering RNA (siRNA), we synthesized 21 bp siRNA duplexes against the MexB gene. RT-PCR was performed to determine whether the siRNA inhibited the expression of MexB mRNA. Changes in antibiotic susceptibility in response to siRNA were measured by the E-test method. The efficacy of siRNAs was determined in a murine model of chronic...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2008

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.00511-08