Outer membrane proteins responsible for the penetration of β-lactams and quinolones in <i>Pseudomonas aeruginosa</i>

Yamano, Yoshinori; Nishikawa, Takafumi; Komatsu, Yoshihide

doi:10.1093/jac/26.2.175

Cited by 24 publications

(20 citation statements)

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“…aeruginosa also produces protein E2 (formerly protein E). The level of this protein was found to be decreased in a mutant showing a wide range of increased resistance to cephalosporins and fluoroquinolones (752). Otherwise, its properties are not known (244).…”

Section: Specific Channelsmentioning

confidence: 98%

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Molecular Basis of Bacterial Outer Membrane Permeability Revisited

Nikaido

2003

Microbiol Mol Biol Rev

3,780

3,800

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Gram-negative bacteria characteristically are surrounded by an additional membrane layer, the outer membrane. Although outer membrane components often play important roles in the interaction of symbiotic or pathogenic bacteria with their host organisms, the major role of this membrane must usually be to serve as a permeability barrier to prevent the entry of noxious compounds and at the same time to allow the influx of nutrient molecules. This review summarizes the development in the field since our previous review (H. Nikaido and M. Vaara, Microbiol. Rev. 49:1-32, 1985) was published. With the discovery of protein channels, structural knowledge enables us to understand in molecular detail how porins, specific channels, TonB-linked receptors, and other proteins function. We are now beginning to see how the export of large proteins occurs across the outer membrane. With our knowledge of the lipopolysaccharide-phospholipid asymmetric bilayer of the outer membrane, we are finally beginning to understand how this bilayer can retard the entry of lipophilic compounds, owing to our increasing knowledge about the chemistry of lipopolysaccharide from diverse organisms and the way in which lipopolysaccharide structure is modified by environmental conditions

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Section: Specific Channelsmentioning

confidence: 98%

“…OprE (earlier named protein E1) was found to be decreased in some P. aeruginosa mutants resistant to cephalosporins carrying double negative charges (752) and was thus thought to be a specific channel. It was then cloned and sequenced (751).…”

Section: Specific Channelsmentioning

confidence: 99%

Molecular Basis of Bacterial Outer Membrane Permeability Revisited

Nikaido

2003

Microbiol Mol Biol Rev

3,780

3,800

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“…Presently, data suggesting that OprF is a porin that leads to antibiotic resistance (35,38,45) and also that OprF is not a porin and is not responsible for antibiotic resistance exist (4,47). We plan to test our hypothesis regarding the structural role of OprF as well as its role in fluoroquinolone uptake and antibiotic resistance by inserting an expression vector containing the cloned OprF gene into our laboratory-derived fluoroquinolone-resistant isolates and testing for function.…”

Section: Discussionmentioning

confidence: 99%

“…Genetic characterization by DNA sequencing of gyrA from E. coli reveals that mutations leading to fluoroquinolone resistance are clustered within a narrow region between nucleotides 199 (Ala-67) and 318 (Gln-106) (21). It has been suggested that mutants possessing a single nucleotide change (point mutation) produce single changes in amino acid sequence which result in an altered DNA gyrase which either reduces the affinity of the fluoroquinolone for the enzyme or blocks the access of the antibiotic to the DNA-DNA gyrase complex (21,39).In addition to DNA gyrase changes, fluoroquinolone resistance in P. aeruginosa can occur as a result of alterations in the outer membrane (2,3,12,14,20,27,31,38,45,46). Resistance selection with fluoroquinolones results in many instances in changes in outer membrane proteins and is manifested as not only resistance to fluoroquinolones but multiple antibiotic resistance (Mar) including beta-lactams, tetracyclines, and chloramphenicol (2,3,12,27,37,38).…”

mentioning

confidence: 99%

“…In addition to DNA gyrase changes, fluoroquinolone resistance in P. aeruginosa can occur as a result of alterations in the outer membrane (2,3,12,14,20,27,31,38,45,46). Resistance selection with fluoroquinolones results in many instances in changes in outer membrane proteins and is manifested as not only resistance to fluoroquinolones but multiple antibiotic resistance (Mar) including beta-lactams, tetracyclines, and chloramphenicol (2,3,12,27,37,38).…”

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confidence: 99%

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Development of multiple-antibiotic-resistant (Mar) mutants of Pseudomonas aeruginosa after serial exposure to fluoroquinolones

Zhanel

Karlowsky

Saunders

et al. 1995

Antimicrob Agents Chemother

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Laboratory-derived fluoroquinolone-resistant mutants were created by serially passaging wild-type Pseudomonas aeruginosa on fluoroquinolone-containing agar to obtain high-level fluoroquinolone resistance (e.g., ciprofloxacin MIC of 1,024 g/ml). With increases of 4-to 32-fold in MICs of fluoroquinolones, these organisms demonstrated (relative to wild-type) normal morphology, resistance to fluoroquinolones only, no change in fluoroquinolone uptake, and no change in lipopolysaccharide profiles or outer membrane protein profiles. Complementation with wild-type Escherichia coli gyrA restored fluoroquinolone susceptibility, suggesting that these were gyrA mutants. After 4-to 32-fold increases in fluoroquinolone MICs (with continued passage on fluoroquinolone-containing agar) isolates demonstrated altered morphology, a multiple-antibioticresistant (Mar) phenotype (including cross-resistance to beta-lactams, chloramphenicol, and tetracycline), reduced fluoroquinolone uptake and altered outer membrane proteins (reductions in the 25-and 38-kDa bands as well as several bands in the 43-to 66-kDa region). Complementation with wild-type E. coli gyrA partially reduced the level of fluoroquinolone resistance by approximately 8-to 32-fold, suggesting that these mutants displayed both gyrA and non-gyrA mutations.Fluoroquinolones such as ciprofloxacin, norfloxacin, and ofloxacin have potent broad-spectrum antibiotic activities against various gram-positive and gram-negative organisms, including Pseudomonas aeruginosa (21, 23). Fluoroquinolones are known to bind to a DNA gyrase-DNA complex as the intracellular target of these drugs (41, 42). In Escherichia coli, DNA gyrase consists of two A and two B subunits (products of the gyrA and gyrB genes, respectively) and is responsible for catalyzing topological changes in DNA, which serves important functions in DNA replication, transcription, recombination, and repair (6, 21). Inhibition of bacterial DNA gyrase by fluoroquinolones leads to inhibition of DNA synthesis which ultimately leads to cell death (11). The precise explanation of the molecular interactions leading to inhibition of DNA gyrase by fluoroquinolones and to cell death is unknown (43).Fluoroquinolone resistance in P. aeruginosa as a result of mutation has been associated with modification of DNA gyrase and/or alteration in outer membrane permeability (2-4, 7, 10, 12, 14, 20, 24, 27, 29-31, 38, 45, 46). It has been indirectly demonstrated that mutations conferring fluoroquinolone resistance in P. aeruginosa may be due to alterations in DNA gyrase, because of the reduced sensitivity to fluoroquinolone inhibition of DNA supercoiling in fluoroquinolone-resistant isolates (10,22,29) and reduced inhibition of DNA synthesis by fluoroquinolone-resistant isolates upon exposure to fluoroquinolones (3, 4, 24). More definitive evidence that fluoroquinolone-resistant mutations in DNA gyrase may be due to alterations in gyrA comes from complementation studies in which wild-type gyrA from E. coli was expressed in fluoroquinoloneresist...

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Susceptibility and Resistance of Pseudomonas aeruginosa to Antimicrobial Agents

Bellido

Hancock

1993

Pseudomonas Aeruginosa as an Opportunistic Pathogen

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Outer membrane proteins responsible for the penetration of β-lactams and quinolones in Pseudomonas aeruginosa

Cited by 24 publications

References 0 publications

Molecular Basis of Bacterial Outer Membrane Permeability Revisited

Molecular Basis of Bacterial Outer Membrane Permeability Revisited

Development of multiple-antibiotic-resistant (Mar) mutants of Pseudomonas aeruginosa after serial exposure to fluoroquinolones

Susceptibility and Resistance of Pseudomonas aeruginosa to Antimicrobial Agents

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