Method or agent for inhibiting the function of efflux pump...

Drug – bio-affecting and body treating compositions – Immunoglobulin – antiserum – antibody – or antibody fragment,... – Monoclonal antibody or fragment thereof

Reexamination Certificate

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C530S388400

Reexamination Certificate

active

07985410

ABSTRACT:
The purpose of the present invention is to provide a method and an agent to efficiently inhibit the function of the drug efflux pump ofPseudomonas aeruginosa. The invention provides a method to inhibit the function of the drug efflux pump ofPseudomonas aeruginosa, comprising modifying any amino acid residue selected from 100th to 109th or 311th to 320th amino acid residues in the amino acid sequence of mature OprM protein. The invention also provides an agent having such inhibitory effect, and a screening method thereof.

REFERENCES:
patent: 2003/0092720 (2003-05-01), Nakayama et al.
patent: 2002510463 (2002-04-01), None
patent: 2003511074 (2003-03-01), None
patent: W09961021 (1999-12-01), None
Gotoh et al (Antimicrobial Agents and Chemotherapy, 42(8):1938-1943, 1998).
Gotoh et al (FEMS Microbiology Letters, 122(3):309-312, 1994).
Jo, et al., Aminoglycoside Efflux inPseudomonas aeruginosa: Involvement of Novel Outer Membrane Proteins, Antimicrobial Agents and Chemotherapy, Mar. 2003, p. 1101-1111, vol. 47, No. 3.
Li, et al., Mutational analysis of the OprM outer membrane component of the MexA-MexB-OprM multidrug efflux system ofPseudomonas aeruginosa, J Bacteriol. Jan. 2001;183(1), p. 12-27.
Wong, et al., Insertion Mutagenesis and Membrane Topology Model of thePseudomonas aeruginosaOuter Membrane Protein OprM, Journal of Bacteriology, May 2000, p. 2402-2410, vol. 182, No. 9.
Wong, et al., Evaluation of a Structural Model ofPseudomonas aeruginosaOuter Membrane Protein OprM, an Efflux Component Involved in Intrinsic Antibiotic Resistance, Journal of Bacteriology, Jan. 2001, p. 367-374, vol. 183, No. 1.
Akama, et al., Crystal structure of the drug discharge outer membrane protein, OprM, ofPseudomonas aeruginosa: dual modes of membrane anchoring and occluded cavity end., J Biol Chem. Dec. 17, 2004; 279 (51):52816-52819.

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