Outer membrane permeability of imipenem in comparison with other .BETA.-lactam antibiotics.

Hashizume, Takashi; Yamaguchi, Akihito; Sawai, Tetsuo

doi:10.7164/antibiotics.39.153

Cited by 4 publications

(4 citation statements)

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“…This change in the PBP pattern is believed to be associated with imipenem resistance,, because repeated passages of isolate 470 in antibiotic-free broth were accompanied with partial recovery of initial susceptibility together with restoration of imipenem-binding to PBP-4. Even though previous investigations seemed to indicate a good correlation between the activity of imipenem and its affinity for PBP-2 (Hashizume, Yamaguchi & Sawai, 1986), the present study showed that PBP-4 had a high binding affinity for imipenem. Moreover, the function of PBP-4 in bacteria other than Escherichia coli is largely unknown and it may be that this target is essential in P. aeruginosa.…”

Section: Discussioncontrasting

confidence: 38%

“…Such resistance emerged in six of ten cases of nosocomial pseudomonal pneumonia (Salata et al, 1985). This inconvenience was encountered even though imipenem is thought to overcome /Mactamase mediated hydrolysis and the permeability barriers of the Gram-negative cell efficiently (Yoshimura, Zalman & Nikaido, 1983;Yoshimura & Nikaido, 1985;Hashizume, Yamaguchi & Sawai, 1986). These are the two major mechanisms of resistance to 0-lactam antibiotics in non-fastidious Gram-negative rods.…”

Section: Introductionmentioning

confidence: 99%

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Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate

Bellido

Veuthey

Blaser

et al. 1990

J Antimicrob Chemother

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Section: Discussioncontrasting

confidence: 38%

Section: Introductionmentioning

confidence: 99%

Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate

Bellido

Veuthey

Blaser

et al. 1990

J Antimicrob Chemother

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“…The influence of EDTA (0.5 and 0.25 the MIC), a compound that increases the outer membrane permeability Of bacteria (31,32), on the MIC of imipenem was determined by the NCCLS macrodilution broth method (12). The influence of EDTA (0.5 and 0.25 the MIC), a compound that increases the outer membrane permeability Of bacteria (31,32), on the MIC of imipenem was determined by the NCCLS macrodilution broth method (12).…”

Section: (28)mentioning

confidence: 99%

Mechanism of imipenem resistance acquired by threePseudomonas aeruginosa strains during imipenem therapy

Vurma-Rapp

Kayser

Hadorn

et al. 1990

Eur. J. Clin. Microbiol. Infect. Dis.

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Imipenem sensitive pretherapy isolates (MICs 1-2 mg/l) and the corresponding resistant posttherapy isolates (MICs 16 mg/l) of Pseudomonas aeruginosa from three patients undergoing imipenem treatment were analyzed to establish the resistance mechanism. The identity of pyocin types, serotypes, DNA restriction endonuclease profiles and plasmid profiles strongly suggested isogenicity of pre- and posttherapy isolates. The imipenem resistant posttherapy isolates showed cross-resistance only to another carbapenem, meropenem. There were neither qualitative nor quantitative differences between pre- and posttherapy isolates in beta-lactamase production. Affinity of the penicillin-binding proteins 1A, 1B, 2, 3, 4,4' and 5 for [14C]imipenem was the same in pre- and posttherapy isolates. One-dimensional and two-dimensional gel electrophoresis of outer membrane protein preparations showed diminished expression of an outer membrane protein of about 46.5 and 47.5 kilodaltons, respectively, in the posttherapy isolates. This protein had an apparent isoelectric point of about pH 5.2 in two-dimensional gel electrophoresis. Growth in proteose peptone no. 2 broth did not reduce expression of this outer membrane protein, which spoke against its identity with the outer membrane protein D1. The permeability of the outer membrane for imipenem was reduced in the posttherapy isolates, since addition of 0.5 or 0.25 of the MIC of the permeabilizing agent ethylene-diaminetetraacetate reduced the MICs of imipenem for all isolates from each patient to the same (susceptible) level. The diminished expression of one of the outer membrane proteins might be the reason for this reduced permeability.

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“…Cefoxitin's initial effectiveness led to a recognized pattern of clinical overuse that may have contributed to the development of resistant ␤-lactamases (5). In addition, reduced permeability contributed to cephamycin resistance in Enterobacteriaceae (6).…”

mentioning

confidence: 99%

Analysis of the Structure and Function of FOX-4 Cephamycinase

Lefurgy

Malashkevich

Aguilan

et al. 2016

Antimicrob Agents Chemother

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j Class C ␤-lactamases poorly hydrolyze cephamycins (e.g., cefoxitin, cefotetan, and moxalactam). In the past 2 decades, a new family of plasmid-based AmpC ␤-lactamases conferring resistance to cefoxitin, the FOX family, has grown to include nine unique members descended from the Aeromonas caviae chromosomal AmpC. To understand the basis for the unique cephamycinase activity in the FOX family, we determined the first X-ray crystal structures of FOX-4, apo enzyme and the acyl-enzyme with its namesake compound, cefoxitin, using the Y150F deacylation-deficient variant. Notably, recombinant expression of Nterminally tagged FOX-4 also yielded an inactive adenylylated enzyme form not previously observed in ␤-lactamases. The posttranslational modification (PTM), which occurs on the active site Ser64, would not seem to provide a selective advantage, yet might present an opportunity for the design of novel antibacterial drugs. Substantial ligand-induced changes in the enzyme are seen in the acyl-enzyme complex, particularly the R2 loop and helix H10 (P289 to N297), with movement of F293 by 10.3 Å. Taken together, this study provides the first picture of this highly proficient class C cephamycinase, uncovers a novel PTM, and suggests a possible cephamycin resistance mechanism involving repositioning of the substrate due to the presence of S153P, N289P, and N346I substitutions in the ligand binding pocket.

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Outer membrane permeability of imipenem in comparison with other .BETA.-lactam antibiotics.

Cited by 4 publications

References 1 publication

Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate

Novel resistance to imipenem associated with an altered PBP-4 in a Pseudomonas aeruginosa clinical isolate

Mechanism of imipenem resistance acquired by threePseudomonas aeruginosa strains during imipenem therapy

Analysis of the Structure and Function of FOX-4 Cephamycinase

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