Resistance to β-Lactam Antibiotics inPseudomonas aeruginosa Due to Interplay between the MexAB-OprM Efflux Pump and β-Lactamase

ABSTRACT We evaluated the roles of the MexAB-OprM efflux pump and β-lactamase in β-lactam resistance in Pseudomonas aeruginosa by constructing OprM-deficient, OprM basal level, and OprM fully expressed mutants from β-lactamase-negative, -inducible, and -overexpressed strains. We conclude that, with the notable exception of imipenem, the MexAB-OprM pump contributes significantly to β-lactam resistance in both β-lactamase-negative and β-lactamase-inducible strains, while the contribution of the MexAB-OprM efflux system is negligible in strains with overexpressed β-lactamase. Overexpression of the efflux pump alone contributes to the high level of β-lactam resistance in the absence of β-lactamase.

[1]  N. Masuda,et al.  Interplay between Chromosomal β-Lactamase and the MexAB-OprM Efflux System in Intrinsic Resistance to β-Lactams inPseudomonas aeruginosa , 1999, Antimicrobial Agents and Chemotherapy.

[2]  N. Gotoh,et al.  Characterization of MexE–MexF–OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa , 1997, Molecular microbiology.

[3]  H. Yoneyama,et al.  The role of mex-gene products in antibiotic extrusion in Pseudomonas aeruginosa. , 1997, Biochemical and biophysical research communications.

[4]  K. Poole,et al.  Overexpression of the mexC–mexD–oprJ efflux operon in nfxB‐type multidrug‐resistant strains of Pseudomonas aeruginosa , 1996, Molecular microbiology.

[5]  H. Yoneyama,et al.  Expression of genes associated with antibiotic extrusion in Pseudomonas aeruginosa. , 1995, Biochemical and biophysical research communications.

[6]  K. Poole,et al.  Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon , 1993, Journal of bacteriology.

[7]  D. Heinrichs,et al.  Cloning and sequence analysis of an EnvCD homologue in Pseudomonas aeruginosa: regulation by iron and possible involvement in the secretion of the siderophore pyoverdine , 1993, Molecular microbiology.

[8]  T. Nakae,et al.  Ofloxacin-resistant Pseudomonas aeruginosa mutants with elevated drug extrusion across the inner membrane. , 1991, Biochemical and Biophysical Research Communications - BBRC.

[9]  H. Yoneyama,et al.  Role of OmpD2 and chromosomal beta-lactamase in carbapenem resistance in clinical isolates of Pseudomonas aeruginosa. , 1991, The Journal of antimicrobial chemotherapy.

[10]  D. Livermore,et al.  Invalidity for Pseudomonas aeruginosa of an accepted model of bacterial permeability to beta-lactam antibiotics , 1991, Antimicrobial Agents and Chemotherapy.

[11]  H. Fukuda,et al.  New norfloxacin resistance gene in Pseudomonas aeruginosa PAO , 1990, Antimicrobial Agents and Chemotherapy.

[12]  H. Nikaido Outer membrane barrier as a mechanism of antimicrobial resistance , 1989, Antimicrobial Agents and Chemotherapy.

[13]  S. Mitsuhashi,et al.  Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa , 1987, Antimicrobial Agents and Chemotherapy.

[14]  A. J. Godfrey,et al.  Resistance of Pseudomonas aeruginosa mutants with altered control of chromosomal beta-lactamase to piperacillin, ceftazidime, and cefsulodin , 1984, Antimicrobial Agents and Chemotherapy.

[15]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[16]  D. Haas,et al.  Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes , 1982, Antimicrobial Agents and Chemotherapy.