Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa

@article{Masuda2000SubstrateSO,
  title={Substrate Specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM Efflux Pumps in Pseudomonas aeruginosa},
  author={Nobuhisa Masuda and Eiko Sakagawa and Satoshi Ohya and Naomasa Gotoh and Hideto Tsujimoto and Takeshi Nishino},
  journal={Antimicrobial Agents and Chemotherapy},
  year={2000},
  volume={44},
  pages={3322 - 3327}
}
ABSTRACT 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 the constructed mutants to 52 antimicrobial agents belonging to various groups suggested the… Expand
Differential Impact of MexB Mutations on Substrate Selectivity of the MexAB-OprM Multidrug Efflux Pump of Pseudomonas aeruginosa
TLDR
It appears that either proper assembly of the MexAB-OprM trimer is necessary for OprM interaction or OPRM association with an unstable MexB trimer might stabilize it, thereby restoring activity. Expand
MexXY RND pump of Pseudomonas aeruginosa PA7 effluxes bi-anionic β-lactams carbenicillin and sulbenicillin when it partners with the outer membrane factor OprA but not with OprM.
TLDR
The results show that by partnering with different OMF proteins MexY can expand its substrate profile, for the first time, that the substrate profile of the MexXY system from P. aeruginosa PA7 can vary depending on which OM factor (OprM or OprA) it complexes with. Expand
Extrusion of Penem Antibiotics by Multicomponent Efflux Systems MexAB-OprM, MexCD-OprJ, and MexXY-OprM of Pseudomonas aeruginosa
ABSTRACT The high intrinsic penem resistance of Pseudomonas aeruginosa is due to the interplay among the outer membrane barrier, the active efflux system MexAB-OprM, and AmpC β-lactamase. We studiedExpand
Aminoglycoside Efflux in Pseudomonas aeruginosa: Involvement of Novel Outer Membrane Proteins
TLDR
OpmG is a major outer membrane efflux channel involved in aminoglycoside efflux in P. aeruginosa PAK and that OpmI, its most related paralog, may share an overlapping function. Expand
Alterations of susceptibility of Pseudomonas aeruginosa by overproduction of multidrug efflux systems, MexAB-OprM, MexCD-OprJ, and MexXY/OprM to carbapenems: substrate specificities of the efflux systems
  • K. Okamoto, N. Gotoh, T. Nishino
  • Biology, Medicine
  • Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy
  • 2002
Abstract Overproduction of multidrug efflux systems MexAB-OprM, MexCD-OprJ, and MexXY/OprM of Pseudomonas aeruginosa caused reduction of susceptibility of the mutant, which lacked AmpC and all threeExpand
The substrate specificity of tripartite efflux systems of Pseudomonas aeruginosa is determined by the RND component.
TLDR
MexB and MexD are primary components of the efflux system responsible for sorting extrusion substrates in Pseudomonas aeruginosa and are shown to be due to extrusion from the chimeric effluxSystem. Expand
Assembly of the MexAB-OprM Multidrug Efflux System of Pseudomonas aeruginosa: Identification and Characterization of Mutations in mexA Compromising MexA Multimerization and Interaction with MexB
TLDR
All but one of the MexA mutations studied compromised MexA-MexB association, suggesting that native structure and/or proper assembly of the protein may be necessary for this interaction with its RND component, MexB. Expand
Clinical Strains of Pseudomonas aeruginosa Overproducing MexAB-OprM and MexXY Efflux Pumps Simultaneously
TLDR
Data show that clinical isolates are able to broaden their drug resistance profiles by coexpressing two Mex efflux pumps and suggest the existence of additional regulators for MexAB-OprM and MexXY. Expand
A Two-Component Regulatory System Interconnects Resistance to Polymyxins, Aminoglycosides, Fluoroquinolones, and β-Lactams in Pseudomonas aeruginosa
TLDR
The data indicate that ParRS may promote either induced or constitutive multidrug resistance to four different classes of antibiotics through the activation of three distinct mechanisms (efflux, porin loss, and LPS modification). Expand
Resistance and Virulence of Pseudomonas aeruginosa Clinical Strains Overproducing the MexCD-OprJ Efflux Pump
TLDR
Data show that, while rather infrequent among P. aeruginosa strains with low-level resistance to ciprofloxacin, MexCD-OprJ-overproducing mutants may be isolated after single therapy with fluoroquinolones and may be pathogenic. Expand
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TLDR
The notion that mexA-mexB-oprK proteins contribute to the intrinsic resistance of P. aeruginosa through the multidrug active efflux process is supported. Expand
Contribution of the MexX-MexY-OprM Efflux System to Intrinsic Resistance in Pseudomonas aeruginosa
TLDR
The results suggest that MexXY induced by these agents is functionally associated with spontaneously expressed OprM and contributes to the intrinsic resistance to these agents. Expand
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TLDR
Transformation of the oprJ mutant with an OprM-expression plasmid decreased the former's susceptibility to the levels exhibited by the nfxB mutant without affecting the substrate specificity of MexCD-OprJ. Expand
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Characterization of mutants lacking themexA-mexB-oprM region clearly indicated that the MexC-MexD-OprJ efflux system is involved in resistance to the ordinary cephems as well as fluoroquinolones and the fourth-generation cEPhems but not to carbenicillin and aztreonam. Expand
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TLDR
Two chimeric pumps were active in antibiotic efflux, as evidenced by their contributions to resistance to a variety of antimicrobial agents, although there was no change in resistance profiles relative to the native pumps, indicating that OprM is not the determining factor for the beta-lactam specificity of MexAB-OprM. Expand
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TLDR
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TLDR
The results suggest that the extrusion of antibiotics occurs most efficiently with a whole assembly of MexA/B-OprM, but it remains a possibility that OprM interacts with a putative inner membrane pump(s). Expand
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TLDR
Data indicate that the multidrug resistance of nfxB strains is due to overexpression of an efflux operon, mexC–mexD–oprJ, encoding components of a second efflux pump in P. aeruginosa. Expand
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TLDR
The results suggest that the extrusion of antibiotics occurs most efficiently with a whole assembly of MexA/B-OprM, but it remains a possibility that OprM interacts with a putative inner membrane pump(s). Expand
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