Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mechanisms of resistance to pefloxacin were investigated in four isogenic Pseudomonas aeruginosa strains: S (parent isolate; MIC, 2 micrograms/ml), PT1 and PT2 (posttherapy isolates obtained in animals; MICs, 32 and 128 micrograms/ml, respectively), and PT2-r (posttherapy isolate obtained after six in vitro subpassages of PT2; MIC, 32 micrograms/ml). [2-3H]adenine incorporation (indirect evidence of DNA gyrase activity) in EDTA-permeabilized cells was less affected by pefloxacin in PT2 and PT2-r (50% inhibitory concentration, 0.27 and 0.26 microgram/ml, respectively) than it was in S and PT1 (50% inhibitory concentration, 0.04 and 0.05 microgram/ml, respectively). Reduced [14C]pefloxacin labeling of intact cells in strains PT1 and PT2 correlated with more susceptibility to EDTA and the presence of more calcium (P less than 0.05) and phosphorus in the outer membrane fractions. Outer membrane protein analysis showed reduced expression of protein D2 (47 kDa) in strains PT1 and PT2. Other proteins were apparently similar in all strains. The addition of calcium chloride (2 mM) to the sodium dodecyl sulfate-solubilized samples of outer membrane proteins, before heating and Western blotting, probed with monoclonal antibody anti-OmpF showed electrophoretic mobility changes of OmpF in strains PT1 and PT2 which were not seen in strain S. Calcium-induced changes were reversed with ethyleneglycoltetraacetate. Decreased [14C]pefloxacin labeling was further correlated with an altered lipopolysaccharide pattern and increased 3-deoxy-D-mannooctulosonic acid concentration (P less than 0.01). These findings suggested that resistance to pefloxacin is associated with altered DNA gyrase in strain PT2-r, with altered permeability in PT1, and with both mechanisms in PT2. The decreased expression of protein D2 and the higher calcium and lipopolysaccharide contents of the outer membrane could be responsible for the permeability deficiency in P. aeruginosa.
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PMID:Resistance to pefloxacin in Pseudomonas aeruginosa. 164 9

The mechanisms of persistence to ciprofloxacin in nine sets of Pseudomonas aeruginosa strains isolated during ciprofloxacin therapy of chronic lung infections in cystic fibrosis patients were studied. Low to moderate levels of ciprofloxacin resistance developed in each case. Each set of pretherapy ciprofloxacin-susceptible, during-therapy ciprofloxacin-resistant, and posttherapy ciprofloxacin-susceptible isolates were shown to be genotypically related by using a radiolabeled epidemiological gene probe. All ciprofloxacin-resistant isolates were found to have altered susceptibilities to both nalidixic acid and various chemically unrelated antibiotics. Analysis of possible resistance mechanisms showed that the strains had altered outer membrane protein or lipopolysaccharide profiles. Complementation of possible DNA gyrase mutations with a plasmid-borne, wild-type Escherichia coli gyrA gene indicated that altered DNA gyrase was at least partly responsible for ciprofloxacin resistance in all strains tested. Attempts to generate ciprofloxacin-susceptible revertants in vitro showed that in some strains reversion was rapid in the absence of ciprofloxacin, while in other strains it was not possible to generate revertants. These data indicate that persistence of Pseudomonas aeruginosa to ciprofloxacin involves changes in DNA gyrase and is associated with pleiotropic changes in outer membrane proteins and lipopolysaccharide.
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PMID:Persistence mechanisms in Pseudomonas aeruginosa from cystic fibrosis patients undergoing ciprofloxacin therapy. 165 66

The mechanism of persistence was characterized in Pseudomonas aeruginosa isolates obtained ten days before (4405), on the tenth day of (4419), and four days after (4478) ciprofloxacin therapy in a cystic fibrosis patient. Isolate 4419 showed a 16-fold increase in resistance to ciprofloxacin, norfloxacin and nalidixic acid. The outer membrane of 4419 had no detectable protein F. A modified lipopolysaccharide profile, a longer lag phase before growth and a slower generation time were also noted for isolate 4419. Cell surface hydrophobicity was increased by 20% in 4419 whereas uptake of [14C]ciprofloxacin was equivalent in all three isolates. Ciprofloxacin doses causing 50% inhibition of DNA synthesis were proportional to MICs for each isolate indicating that the DNA gyrase of 4419 was resistant to quinolones. A quinolone-susceptible revertant of 4419 remained deficient in protein F. Protein F-deficiency was not associated with resistance to quinolones, nor to other antibiotics, supporting the view that it plays little role in outer membrane permeability to antibiotics.
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PMID:Persistence of Pseudomonas aeruginosa during ciprofloxacin therapy of a cystic fibrosis patient: transient resistance to quinolones and protein F-deficiency. 211 39

Decreasing susceptibility to ciprofloxacin was investigated in sequential clinical isolates of Pseudomonas aeruginosa from a patient on ciprofloxacin therapy. All isolates were verified as the same strain by DNA probe. MICs of all quinolones tested were 16- to 32-fold higher for the posttherapy isolates; nonquinolone MICs were unchanged. The isolates were compared by analyses of outer membrane proteins and lipopolysaccharide composition, antimicrobial susceptibilities, measurement of accumulation of ciprofloxacin, and inhibition of DNA gyrase activity by ciprofloxacin and nalidixic acid. No significant changes in outer membrane proteins or ciprofloxacin accumulation were observed; however, both posttherapy isolates lost the long chain O-polysaccharide component of lipopolysaccharide. Preparations of DNA gyrase from the quinolone-resistant posttherapy isolates were 16- to 32-fold less sensitive to inhibition of supercoiling by ciprofloxacin and nalidixic acid than was gyrase from the pretherapy isolate. Inhibition studies on combinations of heterologous gyrase subunits showed that decreased inhibition was conferred by the resistant gyrase A subunits. Thus, acquired resistance to ciprofloxacin in this strain involved an alteration in the A subunit of DNA gyrase and was associated with changes in lipopolysaccharide.
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PMID:Analysis of acquired ciprofloxacin resistance in a clinical strain of Pseudomonas aeruginosa. 215 77

DR-3355, the S-(-)-isomer of ofloxacin, possessed generally twice higher activity than ofloxacin, and its action was bactericidal. The difference in antibacterial activity of these compounds was attributable to their inhibitory activity against DNA gyrase. DR-3355 was characterized by its higher potency against gram-positive cocci and obligate anaerobes than ofloxacin and ciprofloxacin. DR-3355 was somewhat less potent than ciprofloxacin against Enterobacteriaceae and Pseudomonas aeruginosa, but was active against organisms resistant to cefteram, ceftazidime, and amikacin. The activity of DR-3355 was decreased by gyrA mutation, like that of the other quinolones, although it did not alter significantly by deficiency of outer membrane protein F or lipopolysaccharide. Moderately norfloxacin-resistant isolates of Staphylococcus aureus remained susceptible to DR-3355, but not to ciprofloxacin.
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PMID:In vitro antibacterial activity of DR-3355, the S-(-)-isomer of ofloxacin. 217 62

Recently documented antibacterial effects of quinolones are reviewed. DNA gyrase is most likely to be the primary target site for these agents. Quinolones rapidly kill susceptible bacteria; the mechanisms of the bactericidal activity, still poorly understood, probably involve new protein synthesis. Quinolones alter membrane integrity before cell death, leading to leakage of cytoplasmic constituents. In Gram-negative bacteria, quinolones act as chelating agents for outer membrane divalent cations, disorganizing the bacterial lipopolysaccharide layer and facilitating the further entry of quinolone molecules in a 'self-promoted' pathway. Quinolones inhibit plasmid replication and reduce the efficacy of plasmid conjugation. Subinhibitory concentrations of quinolones can interfere with bacterial virulence factors, such as bacterial adherence to the host cell, phagocytosis and production of enzymes implicated in virulence. Recent studies also indicate synergism of quinolones with oxacillin against methicillin-resistant staphylococci and describe improved activity of newer compounds against Gram-positive pathogens.
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PMID:Usual and unusual antibacterial effects of quinolones. 217 6

Amifloxacin showed potent inhibitory activity against DNA gyrase of Escherichia coli. The difference in the susceptibilities of lipopolysaccharide-deficient Salmonella typhimurium mutants and their parent strain was less than twofold, and the difference in the susceptibilities of porin-deficient E. coli mutants and their parent strain was less than twofold. There was cross resistance among the quinolone group of agents; however, the decrease in MIC for norB mutants was slightly lower than that of other fluoroquinolones. Cell lysis was induced with combined treatment of amifloxacin and sodium dodecyl sulfate in E. coli. The frequency of mutants spontaneously resistant to amifloxacin was extremely low in all species tested.
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PMID:In vitro activity of amifloxacin against outer membrane mutants of the family Enterobacteriaceae and frequency of spontaneous resistance. 255 11

We isolated spontaneous mutants from Escherichia coli K-12 with low-level resistance to norfloxacin. These mutants were classified into the following three types on the basis of their properties: (i) NorA appeared to result for mutation in the gyrA locus for the A subunit of DNA gyrase; (ii) NorB showed low-level resistance to quinolones and other antimicrobial agents (e.g., cefoxitin, chloramphenicol, and tetracycline), and the norB gene was considered to map at about 34 min on the E. coli K-12 chromosome; (iii) NorC was less susceptible to norfloxacin and ciprofloxacin but was hypersusceptible to hydrophobic quinolones such as nalidixic acid and rosoxacin, hydrophobic antibiotics, dyes, and detergents. Susceptibility to bacteriophages and the hydrophobicity of the NorC cell surface also differed from that of the parent strain. The norC gene was located near the lac locus at 8 min on the E. coli K-12 chromosome. Both NorB and NorC mutants had a lower rate of norfloxacin uptake, and it was found that the NorB mutant was altered in OmpF porin and that the NorC mutant was altered in both OmpF porin and apparently in the lipopolysaccharide structure of the outer membrane.
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PMID:Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K-12. 353 44

The interaction between divalent cations and quinolones and the mechanism by which the former antagonizes the antimicrobial activities of the latter were investigated. In the presence of either magnesium or calcium chloride, the MICs of 18 quinolones for Gram-positive and Gram-negative bacteria increased. Accumulation of and inhibition of DNA synthesis by quinolones were decreased in the presence of magnesium chloride while, in the presence of EDTA, there was no increase in the concentration of accumulated quinolone for any of the agents tested. Only with nalidixic acid was there enhancement of the inhibition of DNA synthesis. Chelation of selected quinolones by magnesium was demonstrated with a fluorescence assay which showed that the extent to which fluorescence (consistent with chelation) was enhanced varied with the quinolone. Assessment of the strength of the magnesium-quinolone complexes with the chelating agent EDTA demonstrated that some of the complexes could be broken. Thin layer chromatography of quinolones and quinolone-magnesium complexes provided evidence that the components of the complex were probably combined in a ratio of 1:1 and that reduced intracellular accumulation of the quinolones in the presence of magnesium was unlikely to be due to a complex being too bulky to be taken through the porin channels. In contrast with permeabilizers which are known to utilize the self-promoted uptake pathway, none of the quinolones studied permeabilized Gram-negative bacteria to lysozyme, caused enhanced fluorescence to 1-N-phenyl-naphthylamine (NPN) or increased the leakage of periplasmic beta-lactamase into the culture medium. The reduced activities of the quinolones in the presence of divalent cations may be the result of the chelation of exogenous ions and, possibly, lipopolysaccharide- or lipoteichoic acid-associated magnesium ions, thereby resulting in less drug being available to enter the bacterium. Alternatively, reduced activity may be due to a fundamental effect on the interaction between quinolones and their target DNA gyrase.
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PMID:Interaction of divalent cations, quinolones and bacteria. 786 2

Yersinia enterocolitica is a facultative intracellular parasite, displaying the ability to grow saprophytically or invade and persist intracellularly in the mammalian reticuloendothelial system. The transition between such diverse environments requires the co-ordinated regulation of specific sets of genes on both the chromosome and virulence plasmid. Temperature has a profound pleiotropic effect on gene expression and phenotypically promotes alterations in cell morphology, outer-membrane protein synthesis, urease production, lipopolysaccharide synthesis, motility, and synthesis of genes involved in invasion of eukaryotic host cells. By examining thermoregulated flagella biosynthesis, we have determined that motility is repressed at 25 degrees C (permissive temperature) with subinhibitory concentrations of novobiocin. These conditions also induce virulence gene expression suggesting novobiocin addition simulates, at least partially, a high-temperature environment. Furthermore, temperature-shift experiments, using Y. enterocolitica containing pACYC184 as a reporter plasmid, indicate that thermo-induced alterations of DNA supercoiling coincide with temperature-induced phenotypic changes. A class of putative DNA gyrase mutant (novobiocin resistant) likewise demonstrates the 37 degrees C phenotype when cultured at 25 degrees C; it is non-motile, urease negative, calcium growth dependent, and positive for Yop expression. These results support a model implicating DNA topology as a contributing factor of Y. enterocolitica thermoregulation.
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PMID:Thermoregulation in Yersinia enterocolitica is coincident with changes in DNA supercoiling. 805 44


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