Conservation of the multidrug resistance efflux gene oprM in Pseudomonas aeruginosa.

1997 ◽  
Vol 41 (4) ◽  
pp. 853-856 ◽  
Author(s):  
N Bianco ◽  
S Neshat ◽  
K Poole
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Pseudomonas Syringae ◽  
Genomic Dna ◽  
Resistance Mechanisms ◽  
Pseudomonas Chlororaphis ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Multidrug Resistance Gene ◽  
Multidrug Efflux System

An intragenic probe derived from the multidrug resistance gene oprM hybridized with genomic DNA from all 20 serotypes of Pseudomonas aeruginosa and from all 34 environmental and clinical isolates tested, indicating that the MexA-MexB-OprM multidrug efflux system is highly conserved in this organism. The oprM probe also hybridized with genomic DNA from Pseudomonas aureofaciens, Pseudomonas chlororaphis, Pseudomonas syringae, Burkholderia pseudomallei, and Pseudomonas putida, suggesting that efflux-mediated multidrug resistance mechanisms may be somewhat broadly distributed.

scholarly journals Mutations in PA3574 (nalD) Lead to Increased MexAB-OprM Expression and Multidrug Resistance in Laboratory and Clinical Isolates of Pseudomonas aeruginosa

2005 ◽  
Vol 49 (5) ◽  
pp. 1782-1786 ◽  
Author(s):  
Mara L. Sobel ◽  
Didier Hocquet ◽  
Lily Cao ◽  
Patrick Plesiat ◽  
Keith Poole
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Resistant Mutant ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Clinical Strains ◽  
Transposon Insertion ◽  
Multidrug Efflux System

ABSTRACT Mutations in genes mexR and nalC have previously been shown to drive overexpression of the MexAB-OprM multidrug efflux system in Pseudomonas aeruginosa. A transposon insertion multidrug-resistant mutant of P. aeruginosa overproducing MexAB-OprM was disrupted in yet a third gene, PA3574, encoding a probable repressor of the TetR/AcrR family that we have dubbed NalD. Clinical strains overexpressing MexAB-OprM but lacking mutations in mexR or nalC were also shown to carry mutations in nalD. Moreover, the cloned nalD gene reduced the multidrug resistance and MexAB-OprM expression of the transposon mutant and clinical isolates, highlighting the significance of the nalD mutations vis-à-vis MexAB-OprM overexpression in these isolates.

scholarly journals SmeC, an Outer Membrane Multidrug Efflux Protein of Stenotrophomonas maltophilia

2002 ◽  
Vol 46 (2) ◽  
pp. 333-343 ◽  
Author(s):  
Xian-Zhi Li ◽  
Li Zhang ◽  
Keith Poole
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistance ◽  
Stenotrophomonas Maltophilia ◽  
Promoter Activity ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Regulatory Systems ◽  
Pcr Product ◽  
Two Component ◽  
Multidrug Efflux System

ABSTRACT A homologue of the mexAB-oprM multidrug efflux operon of Pseudomonas aeruginosa, smeABC, was cloned from Stenotrophomonas maltophilia by using, as a probe, a PCR product amplified from this organism with primers based on the mexB sequence. The smeABC genes were hyperexpressed in a mutant strain displaying resistance to several antimicrobials, including aminoglycosides, β-lactams, and fluoroquinolones. Deletions in smeC but not smeB compromised this resistance, suggesting that SmeC contributed to the multidrug resistance of the mutant as part of another, as-yet-unidentified multidrug efflux system. Consistent with SmeC functioning independently of SmeAB, a promoter activity was identified upstream of smeC. Upstream of the smeABC genes, a putative two-gene operon, smeSR, encoding homologues of bacterial two-component regulatory systems was identified. The cloned smeR gene activated expression of a smeA-lacZ fusion, indicating that SmeR positively regulates expression of the smeABC genes. Consistent with this, the multidrug resistance of the SmeABC-hyperexpressing mutant was compromised by deletion of smeR. Intriguingly, SmeC expression in S. maltophilia paralleled a β-lactamase activity provided by a C-terminally truncated L2 enzyme, which was apparently responsible for the β-lactam resistance of the SmeABC-hyperexpressing mutant. This represents the first report of coregulation of an efflux resistance determinant and a β-lactamase.

scholarly journals Meropenem potentiation of aminoglycoside activity against Pseudomonas aeruginosa: involvement of the MexXY-OprM multidrug efflux system

2018 ◽  
Vol 73 (5) ◽  
pp. 1247-1255 ◽  
Author(s):  
Keith Poole ◽  
Christie Gilmour ◽  
Maya A Farha ◽  
Michael D Parkins ◽  
Rachael Klinoski ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Multidrug Efflux System

scholarly journals Multidrug efflux in intrinsic resistance to trimethoprim and sulfamethoxazole in Pseudomonas aeruginosa.

1996 ◽  
Vol 40 (10) ◽  
pp. 2288-2290 ◽  
Author(s):  
T Köhler ◽  
M Kok ◽  
M Michea-Hamzehpour ◽  
P Plesiat ◽  
N Gotoh ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Outer Membrane Proteins ◽  
Multiple Drug ◽  
Drug Efflux ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Intrinsic Resistance ◽  
Wild Type Parent ◽  
Multidrug Efflux System

Pseudomonas aeruginosa possesses at least two multiple drug efflux systems which are defined by the outer membrane proteins OprM and OprJ. We have found that mutants overexpressing OprM were two- and eightfold more resistant than their wild-type parent to sulfamethoxazole (SMX) and trimethoprim (TMP), respectively. For OprJ-overproducing strains, MICs of TMP increased fourfold but those of SMX were unchanged. Strains overexpressing OprM, but not those overexpressing OprJ, became hypersusceptible to TMP and SMX when oprM was inactivated. The wild-type antibiotic profile could be restored in an oprM mutant by transcomplementation with the cloned oprM gene. These results demonstrate that the mexABoprM multidrug efflux system is mainly responsible for the intrinsic resistance of P. aeruginosa to TMP and SMX.

scholarly journals Involvement of the MexXY-OprM Efflux System in Emergence of Cefepime Resistance in Clinical Strains of Pseudomonas aeruginosa

2006 ◽  
Vol 50 (4) ◽  
pp. 1347-1351 ◽  
Author(s):  
Didier Hocquet ◽  
Patrice Nordmann ◽  
Farid El Garch ◽  
Ludovic Cabanne ◽  
Patrick Plésiat
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanism ◽  
Epidemiological Studies ◽  
Teaching Hospitals ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Clinical Strains ◽  
Rnd Transporter ◽  
Multidrug Efflux System

ABSTRACT Cefepime (FEP) and ceftazidime (CAZ) are potent β-lactam antibiotics with similar MICs (1 to 2 μg/ml) for wild-type strains of Pseudomonas aeruginosa. However, recent epidemiological studies have highlighted the occurrence of isolates more resistant to FEP than to CAZ (FEPr/CAZs profile). We thus investigated the mechanisms conferring such a phenotype in 38 clonally unrelated strains collected in two French teaching hospitals. Most of the bacteria (n = 32; 84%) appeared to stably overexpress the mexY gene, which codes for the RND transporter of the multidrug efflux system MexXY-OprM. MexXY up-regulation was the sole FEP resistance mechanism identified (n = 12) or was associated with increased levels of pump MexAB-OprM (n = 5) or MexJK (n = 2), synthesis of secondary β-lactamase PSE-1 (n = 10), derepression of cephalosporinase AmpC (n = 1), coexpression of both OXA-35 and MexJK (n = 1), or production of both PSE-1 and MexAB-OprM (n = 1). Down-regulation of the mexXY operon in seven selected strains by the plasmid-borne repressor gene mexZ decreased FEP resistance from two- to eightfold, thereby demonstrating the significant contribution of MexXY-OprM to the FEPr/CAZs phenotype. The six isolates of this series that exhibited wild-type levels of the mexY gene were found to produce β-lactamase PSE-1 (n = 1), OXA-35 (n = 4), or both PSE-1 and OXA-35 (n = 1). Altogether, these data provide evidence that MexXY-OprM plays a major role in the development of FEP resistance among clinical strains of P. aeruginosa.

scholarly journals Characterization of MexE–MexF–OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa

1997 ◽  
Vol 23 (2) ◽  
pp. 345-354 ◽  
Author(s):  
Thilo Ko¨hler ◽  
Mehri Michéa‐Hamzehpour ◽  
Uta Henze ◽  
Naomasa Gotoh ◽  
Lasta Kocjancic Curty ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Multidrug Efflux System

scholarly journals MexCD-OprJ Multidrug Efflux System of Pseudomonas aeruginosa: Involvement in Chlorhexidine Resistance and Induction by Membrane-Damaging Agents Dependent upon the AlgU Stress Response Sigma Factor

2008 ◽  
Vol 52 (12) ◽  
pp. 4478-4482 ◽  
Author(s):  
Sebastien Fraud ◽  
Aaron J. Campigotto ◽  
Zhilin Chen ◽  
Keith Poole
Keyword(s):  
Gene Expression ◽  
Pseudomonas Aeruginosa ◽  
Stress Response ◽  
Sigma Factor ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Multidrug Efflux System

ABSTRACT The biocide chlorhexidine (CHX) as well as additional membrane-active agents were shown to induce expression of the mexCD-oprJ multidrug efflux operon, dependent upon the AlgU stress response sigma factor. Hyperexpression of this efflux system in nfxB mutants was also substantially AlgU dependent. CHX resistance correlated with efflux gene expression in various mutants, consistent with MexCD-OprJ being a determinant of CHX resistance.

scholarly journals Antibiotic Inducibility of the MexXY Multidrug Efflux System of Pseudomonas aeruginosa: Involvement of the Antibiotic-Inducible PA5471 Gene Product

2006 ◽  
Vol 188 (5) ◽  
pp. 1847-1855 ◽  
Author(s):  
Yuji Morita ◽  
Mara L. Sobel ◽  
Keith Poole
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antimicrobial Resistance ◽  
Antibiotic Exposure ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Translation Process ◽  
Mutant Strains ◽  
Twofold Decrease ◽  
Multidrug Efflux System ◽  
Resistance Mutants

ABSTRACT The MexXY components of the MexXY-OprM multidrug efflux system of Pseudomonas aeruginosa are encoded by a MexZ repressor-regulated operon that is inducible by antibiotics that target the ribosome. Mutant strains disrupted in a gene, PA5471, were shown to be compromised for drug-inducible mexXY expression and, therefore, MexXY-OprM-mediated antimicrobial resistance. The PA5471 gene was inducible by the same ribosome-targeting agents that induce mexXY expression. Moreover, vector-driven expression of cloned PA5471 was sufficient to promote mexXY expression and MexXY-mediated resistance in the absence of antibiotic exposure, consistent with PA5471 directly or indirectly activating mexXY expression following its own upregulation in response to antibiotics. The requirement for PA5471 for mexXY expression and antimicrobial resistance was, however, obviated in mutants lacking the MexZ repressor of mexXY expression, suggesting that PA5471 directly or indirectly modulates MexZ activity in effecting mexXY expression. While the recruitment of PA5471 and MexXY in response to ribosome disruption by antimicrobials is consistent with their genes playing a role in protecting cells from the adverse consequences of disrupting the translation process, reminiscent of trans-translation, these genes appear to operate independently in their contribution to resistance: mutants defective in trans-translation showed a much more modest (twofold) decrease in resistance to ribosome-targeting agents than those lacking PA5471 or MexXY, and this decrease was observed whether functional PA5471/MexXY was present or not.

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