|
|
|
|
|
|
The Magnitude of the Association between Fluoroquinolone Use and Quinolone-Resistant Escherichia coli and Klebsiella pneumoniae May Be Lower than Previously Reported. Maureen K. Bolon, 2004.Case-control analyses of resistant versus susceptible isolates have implicated fluoroquinolone exposure as a strong risk factor for fluoroquinolone-resistant isolates of Enterobacteriaceae . We suspect that such methodology may overestimate this association . A total of 84 cases with fluoroquinolone-resistant isolates and 578 cases with fluoroquinolone-susceptible isolates of Escherichia coli or Klebsiella pneumoniae were compared with 608 hospitalized controls in parallel multivariable analyses . For comparison of previous estimates, the results of 10 published case-control studies of risk for fluoroquinolone resistance in isolates of Enterobacteriaceae were pooled by using a random-effects model . Exposure to fluoroquinolones was significantly positively associated with fluoroquinolone resistance (odds ratio [OR], 3.17) and negatively associated with fluoroquinolone susceptibility (OR, 0.18) . Multivariable analyses yielded similar estimates (ORs, 2.04 and 0.10, respectively) . As data on antibiotic exposure were limited to inpatient prescriptions, misclassification of fluoroquinolone exposure in persons who received fluoroquinolones as outpatients may have led to an underestimation of the true effect size . Pooling the results of previously published studies in which a direct comparison of fluoroquinolone-resistant and fluoroquinolone-susceptible cases was used resulted in a markedly higher effect estimate (OR, 18.7) . Had we directly compared resistant and susceptible cases, our univariate OR for the association between fluoroquinolone use and the isolation of resistant Enterobacteriaceae would have been 19.3, and the multivariate OR would have been 16.5 . Fluoroquinolone use is significantly associated with the isolation of fluoroquinolone-resistant Enterobacteriaceae; however, previous studies likely exaggerated the magnitude of this association . In Vivo Reconstitution of the FhuA Transport Protein of Escherichia coli K-12. Michael Braun, 2003.The FhuA protein in the outer membrane of Escherichia coli actively transports ferrichrome and the antibiotics albomycin and rifamycin CGP 4832 and serves as a receptor for the phages T1, T5, and  80 and for colicin M and microcin J25 . The crystal structure reveals a ß-barrel with a globular domain, the cork, which closes the channel formed by the barrel . Genetic deletion of the cork resulted in a ß-barrel that displays no FhuA activity . A functional FhuA was obtained by cosynthesis of separately encoded cork and the ß-barrel domain, each endowed with a signal sequence, which showed that complementation occurs after secretion of the fragments across the cytoplasmic membrane . Inactive complete mutant FhuA and an FhuA fragment containing 357 N-proximal amino acid residues complemented the separately synthesized wild-type ß-barrel to form an active FhuA . Previous claims that the ß-barrel is functional as transporter and receptor resulted from complementation by inactive complete FhuA and the 357-residue fragment . No complementation was observed between the wild-type cork and complete but inactive FhuA carrying cork mutations that excluded the exchange of cork domains . The data indicate that active FhuA is reconstituted extracytoplasmically by insertion of separately synthesized cork or cork from complete FhuA into the ß-barrel, and they suggest that in wild-type FhuA the ß-barrel is formed prior to the insertion of the cork .
Biotransformation of Hexahydro-1,3,5-Trinitro-1,3,5-Triazine (RDX) by a Rabbit Liver Cytochrome P450: Insight into the Mechanism of RDX Biodegradation by Rhodococcus sp . Strain DN22. Bharat Bhushan, 2003.A unique metabolite with a molecular mass of 119 Da (C2H5N3O3) accumulated during biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Rhodococcus sp . strain DN22 (D . Fournier, A . Halasz, J . C . Spain, P . Fiurasek, and J . Hawari, Appl . Environ . Microbiol . 68:166-172, 2002) . The structure of the molecule and the reactions that led to its synthesis were not known . In the present study, we produced and purified the unknown metabolite by biotransformation of RDX with Rhodococcus sp . strain DN22 and identified the molecule as 4-nitro-2,4-diazabutanal using nuclear magnetic resonance and elemental analyses . Furthermore, we tested the hypothesis that a cytochrome P450 enzyme was responsible for RDX biotransformation by strain DN22 . A cytochrome P450 2B4 from rabbit liver catalyzed a very similar biotransformation of RDX to 4-nitro-2,4-diazabutanal . Both the cytochrome P450 2B4 and intact cells of Rhodococcus sp . strain DN22 catalyzed the release of two nitrite ions from each reacted RDX molecule . A comparative study of cytochrome P450 2B4 and Rhodococcus sp . strain DN22 revealed substantial similarities in the product distribution and inhibition by cytochrome P450 inhibitors . The experimental evidence led us to propose that cytochrome P450 2B4 can catalyze two single electron transfers to RDX, thereby causing double denitration, which leads to spontaneous hydrolytic ring cleavage and decomposition to produce 4-nitro-2,4-diazabutanal . Our results provide strong evidence that a cytochrome P450 enzyme is the key enzyme responsible for RDX biotransformation by Rhodococcus sp . strain DN22 .
|
© 2005
Transgalactic Ltd (manufacturer of Bioscreen C software) |
Privacy Statement | P.O. Box
1393, 00101 Helsinki, Finland,
Last modified: May 25, 2005
| ||||||
