Mechanisms of beta-lactam resistance in british isolates of Pseudomonas aeruginosa

Williams, Ruth; Livermore, David M.; Lindridge, M. A.; Said, A. A.; Williams, John D.

doi:10.1099/00222615-17-3-283

Cited by 70 publications

(40 citation statements)

References 28 publications

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“…Clinical isolates of P. aeruginosa vary extensively in levels of intrinsic resistance (20,45). In the so-called intrinsically carbenicillin-resistant strains, the MICs of tetracycline, chloramphenicol, fluoroquinolones, and also of many ,-lactams may reach very high levels (18,20).…”

Section: Resultsmentioning

confidence: 99%

“…They are altered neither in their 1-lactamases nor in their penicillin-binding proteins (18,45), and this phenotype was often called intrinsic carbenicillin resistance. Since these isolates are also much more resistant to other agents, such as tetracycline, chloramphenicol, and fluoroquinolones (20), in this paper we will call this phenotype elevated intrinsic resistance.…”

mentioning

confidence: 99%

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Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin

Livermore

Nikaido

1994

Antimicrob Agents Chemother

359

267

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Most strains of Pseudomonas aeruginosa are significantly more resistant, even in the absence of R plasmids, to many antimicrobial agents, including P-lactams, tetracycline, chloramphenicol, and fluoroquinolones, than most other gram-negative rods. This broad-range resistance has so far been assumed to be mainly due to the low permeability of the P. aeruginosa outer membrane. The intrinsic-resistance phenotype becomes further enhanced in "intrinsically carbenicillin-resistant" isolates, which were often assumed to produce outer membranes of even lower permeability. It has been shown, however, that this hypothesis cannot explain the f-lactam resistance of these isolates (D. M. Livermore and K. W. M. Davy, Antimicrob. Agents Chemother. 35:916-921, 1991). In this study, we examined the uptake of tetracycline, chloramphenicol, and norfloxacin by intact cells using strains showing widely different levels of intrinsic resistance. Their accumulation and the response to the addition of a proton conductor showed that even relatively susceptible strains of P. aeruginosa actively pump out these compounds from the cell and that the efflux activity becomes much stronger in strains showing higher levels of intrinsic resistance. We conclude that the efilux mechanism(s) are likely to contribute significantly to the intrinsic resistance of P. aeruginosa isolates to tetracycline, chloramphenicol, and fluoroquinolones, as does the low permeability of the outer membrane. This conclusion is supported by the observation that the hypersusceptibility to various agents of the mutant K799/61 (W. Zimmermann, Antimicrob. Agents Chemother. 18:94-100, 1980) was apparently caused by the lack of active eftlux. Although the hypersusceptibility of this mutant has hitherto been assumed to be solely due to its higher outer membrane permeability, its outer membrane was shown to have a coefficient of permeability to cephaloridine that was not significantly different from that of the parent, resistant strain K799/WT. The strains with elevated intrinsic resistance overproduced two cytoplasmic membrane proteins and one outer membrane protein; at least two of these proteins appeared different from the proteins overproduced in the recently described mutant with a derepressed multidrug efilux system, MexA-MexB-OprK (K. Poole, K. Krebes, C. McNally, and S. Neshat, J. Bacteriol. 175:7363-7372, 1993).It is well known that most strains of Pseudomonas aeruginosa show significant degrees of intrinsic resistance to a wide variety of antimicrobial agents, including most ,-lactams, tetracyclines, chloramphenicol, and fluoroquinolones. The outer membrane of this species shows a very low nonspecific permeability to small, hydrophilic molecules (1, 46), and this has generally been thought to be the main cause of the resistance of this organism.Nevertheless, the low outer membrane permeability cannot be the entire explanation of the intrinsic resistance. First, theoretical analysis shows that even the low-permeability outer membrane of this species should allow a suf...

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin

Livermore

Nikaido

1994

Antimicrob Agents Chemother

359

267

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“…Furthermore, the level of intrinsic resistance can be elevated to a much higher level. Thus, almost 80% of the carbenicillin-resistant clinical isolates from the British isles were of this type (54). It was difficult to explain this higher resistance phenotype, because there was no elevation of the periplasmic ␤-lactamase level and because they were more resistant not only to ␤-lactams but also to other agents, such as tetracycline, chloramphenicol, and fluoroquinolones.…”

Section: Multicomponent Multidrug Efflux Systems Of Different Classesmentioning

confidence: 98%

Multidrug efflux pumps of gram-negative bacteria

1996

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“…Thus, Rella and Haas (226) mutated the repressor gene of the mexAB operon to give hyperexpression and showed that the MICs of ciprofloxacin and carbenicillin were increased 8-and 32-fold, respectively. Among carbenicillin-resistant clinical isolates of P. aeruginosa collected in a United Kingdom study in 1982, almost 80% did not produce carbenicillin-hydrolyzing J3-lactamase and appeared to belong to the elevated efflux type (311). Similarly, a study conducted in France showed that approximately one third of ticarcillin-resistant P. aeruginosa isolates had susceptibility patterns that were characteristic of multidrug efflux (24).…”

Section: Reduced Susceptibility To Biocides Associated With Chromosommentioning

confidence: 99%

Potential Impact of Increased Use of Biocides in Consumer Products on Prevalence of Antibiotic Resistance

2003

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There has recently been much controversy surrounding the increased use of antibacterial substances in a wide range of consumer products and the possibility that, as with antibiotics, indiscriminate use of biocides might contribute to the overall pattern of susceptibility in the general environment and in the clinic. Such speculation, based on the isolation of resistant mutants from in vitro monoculture experiments, is not reflected by an emergence of biocide-resistant strains in vivo. This review provides a broad coverage of the biocide and resistance literature and evaluates the potential risks, perceived from such laboratory monoculture experiments, against evidence gathered over 50 years of field studies. An explanation for the continued effectiveness of broad-spectrum biocidal agents against the decline in efficacy of therapeutic agents is provided based on the fitness costs of resistance and the ubiquity of naturally occurring substances that possess antibacterial effect. While we conclude from this review of the literature that the incorporation of antibacterial agents into a widening sphere of personal products has had little or no impact on the patterns of microbial susceptibility observed in the environment, the associated risks remain finite. The use of such products should therefore be associated with a clear demonstration of added value either to consumer health or to the product life. Hygienic products should therefore be targeted to applications for which the risks have been established

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Mechanisms of beta-lactam resistance in british isolates of Pseudomonas aeruginosa

Cited by 70 publications

References 28 publications

Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin

Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: resistance to tetracycline, chloramphenicol, and norfloxacin

Multidrug efflux pumps of gram-negative bacteria

Potential Impact of Increased Use of Biocides in Consumer Products on Prevalence of Antibiotic Resistance

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