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 Polymyxin Susceptibility in Pseudomonas aeruginosa Linked to the MexXY-OprM Multidrug Efflux System

2015 ◽  
Vol 59 (12) ◽  
pp. 7276-7289 ◽  
Author(s):  
Keith Poole ◽  
Calvin Ho-Fung Lau ◽  
Christie Gilmour ◽  
Youai Hao ◽  
Joseph S. Lam
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Resistance Mechanism ◽  
Polymyxin B ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Content Type ◽  
Polymyxin E ◽  
Increased Susceptibility ◽  
Multidrug Efflux System

ABSTRACTThe ribosome-targeting antimicrobial, spectinomycin (SPC), strongly induced themexXYgenes of the MexXY-OprM multidrug efflux system inPseudomonas aeruginosaand increased susceptibility to the polycationic antimicrobials polymyxin B and polymyxin E, concomitant with a decrease in expression of the polymyxin resistance-promoting lipopolysaccharide (LPS) modification loci,arnBCADTEFand PA4773-74. Consistent with the SPC-promoted reduction inarnand PA4773-74 expression being linked tomexXY, expression of these LPS modification loci was moderated in a mutant constitutively expressingmexXYand enhanced in a mutant lacking the efflux genes. Still, the SPC-mediated increase in polymyxin susceptibility was retained in mutants lackingarnBand/or PA4773-74, an indication that their reduced expression in SPC-treated cells does not explain the enhanced polymyxin susceptibility. That the polymyxin susceptibility of a mutant strain lackingmexXYwas unaffected by SPC exposure, however, was an indication that the unknown polymyxin resistance ‘mechanism’ is also influenced by the MexXY status of the cell. In agreement with SPC and MexXY influencing polymyxin susceptibility as a result of changes in the LPS target of these agents, SPC treatment yielded a decline in common polysaccharide antigen (CPA) synthesis in wild-typeP. aeruginosabut not in the ΔmexXYmutant. A mutant lacking CPA still showed the SPC-mediated decline in polymyxin MICs, however, indicating that the loss of CPA did not explain the SPC-mediated MexXY-dependent increase in polymyxin susceptibility. It is possible, therefore, that some additional change in LPS promoted by SPC-inducedmexXYexpression impacted CPA synthesis or its incorporation into LPS and that this was responsible for the observed changes in polymyxin susceptibility.

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 Overexpression of the MexEF-OprN Multidrug Efflux System Affects Cell-to-Cell Signaling in Pseudomonas aeruginosa

2001 ◽  
Vol 183 (18) ◽  
pp. 5213-5222 ◽  
Author(s):  
Thilo Köhler ◽  
Christian van Delden ◽  
Lasta Kocjancic Curty ◽  
Mehri Michea Hamzehpour ◽  
Jean-Claude Pechere
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Efflux Pump ◽  
Homoserine Lactone ◽  
Wild Type ◽  
Multidrug Efflux ◽  
Efflux System ◽  
Sensing Systems ◽  
In The Wild ◽  
Type Mutant ◽  
Regulator Genes

ABSTRACT Intrinsic and acquired antibiotic resistance of the nosocomial pathogen Pseudomonas aeruginosa is mediated mainly by the expression of several efflux pumps of broad substrate specificity. Here we report that nfxC type mutants, overexpressing the MexEF-OprN efflux system, produce lower levels of extracellular virulence factors than the susceptible wild type. These include pyocyanin, elastase, and rhamnolipids, three factors controlled by the las and rhl quorum-sensing systems of P. aeruginosa. In agreement with these observations are the decreased transcription of the elastase genelasB and the rhamnosyltransferase genesrhlAB measured in nfxC type mutants. Expression of the lasR and rhlR regulator genes was not affected in the nfxC type mutant. In contrast, transcription of the C4-homoserine lactone (C4-HSL) autoinducer synthase gene rhlI was reduced by 50% in the nfxC type mutant relative to that in the wild type. This correlates with a similar decrease in C4-HSL levels detected in supernatants of the nfxC type mutant. Transcription of an rhlAB-lacZ fusion could be partially restored by the addition of synthetic C4-HSL andPseudomonas quinolone signal (PQS). It is proposed that the MexEF-OprN efflux pump affects intracellular PQS levels.

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 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 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.

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