Abstract:
:Isoxyl (ISO), a thiourea derivative that was successfully used for the clinical treatment of tuberculosis during the 1960s, is an inhibitor of the synthesis of oleic and mycolic acids in Mycobacterium tuberculosis. Its effect on oleic acid synthesis has been shown to be attributable to its inhibitory activity on the stearoyl-coenzyme A desaturase DesA3, but its enzymatic target(s) in the mycolic acid pathway remains to be identified. With the goal of elucidating the mode of action of ISO, we have isolated a number of spontaneous ISO-resistant mutants of M. tuberculosis and undertaken their genotypic characterization. We report here the characterization of a subset of these strains carrying mutations in the monooxygenase gene ethA. Through complementation studies, we demonstrate for the first time that the EthA-mediated oxidation of ISO is absolutely required for this prodrug to inhibit its lethal enzymatic target(s) in M. tuberculosis. An analysis of the metabolites resulting from the in vitro transformation of ISO by purified EthA revealed the occurrence of a formimidamide allowing the formulation of an activation pathway in which the oxidation of ISO catalyzed by EthA is followed by chemical transformations involving extrusion or elimination and, finally, hydrolysis.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Korduláková J,Janin YL,Liav A,Barilone N,Dos Vultos T,Rauzier J,Brennan PJ,Gicquel B,Jackson Mdoi
10.1128/AAC.00433-07subject
Has Abstractpub_date
2007-11-01 00:00:00pages
3824-9issue
11eissn
0066-4804issn
1098-6596pii
AAC.00433-07journal_volume
51pub_type
杂志文章abstract::The in vivo efficacy of ciprofloxacin or pefloxacin alone or in combination with fosfomycin was evaluated in experimental aortic valve endocarditis induced in 133 rabbits by a multidrug-susceptible or multidrug-resistant strain of Pseudomonas aeruginosa. Therapy was initiated early (12 h after infection), when bacteri...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.2.496
更新日期:1995-02-01 00:00:00
abstract::In a randomized crossover trial, six volunteers received 200- and 400-mg doses of loracarbef (LY 163892), a new oral cephalosporin. Mean +/- standard error of the mean concentrations in serum obtained after 1.5 and 3 h were 13.2 +/- 2.8 and 4.3 +/- 0.7 mg/liter, respectively, after the 400-mg dose and 6.9 +/- 1.0 and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.36.3.521
更新日期:1992-03-01 00:00:00
abstract::The antileprosy effect of rifampin was evaluated by a newly developed rapid in vitro assay wherein 31 human-derived strains and 1 armadillo-derived strain of Mycobacterium leprae were maintained for 2 and 3 weeks, respectively, in murine and human macrophages in the presence of [3H]thymidine. Of these strains, 27 show...
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pub_type: 杂志文章
doi:10.1128/aac.24.4.579
更新日期:1983-10-01 00:00:00
abstract::Norovirus (NoV) is the leading cause of acute gastroenteritis worldwide, causing over 200,000 deaths a year. NoV is nonenveloped, with a single-stranded RNA genome, and is primarily transmitted person to person. The viral RNA-dependent RNA polymerase (RdRp) is critical for the production of genomic and subgenomic RNA ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02799-13
更新日期:2014-06-01 00:00:00
abstract::The dependence of microbial killing on chloride ions present in solutions undergoing iontophoresis is addressed. A 400-microA current was applied to vials containing synthetic urine or saline, and the production of chlorine-based substances (CBSs) was detected by the N,N-diethyl-p-phenylene diamine colorimetric method...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::By the time-kill curve method, the combination of N-formimidoyl thienamycin and gentamicin showed synergism against 47 of 48 strains of enterococci, whereas the combination of N-formimidoyl thienamycin and tobramycin was synergistic against 46 strains. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.6.1082
更新日期:1982-12-01 00:00:00
abstract::A series of quaternary ammonium compounds that are esters of betaine and fatty alcohols with hydrocarbon chain lengths of 10 to 18 carbon atoms were tested with respect to antimicrobial activities and rates of hydrolysis. When the tetradecyl derivative was tested against some selected microorganisms, the killing effec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.10.1949
更新日期:1990-10-01 00:00:00
abstract::The antifolate activity and the transport characteristics of isoaminopterin (IA) in HeLa cells were studied and compared with those of methotrexate (MTX). Both IA and MTX inhibited the incorporation of [2-(14)C]deoxyuridine into HeLa cell DNA by 50% at a concentration of 0.09 muM by 8 h postaddition of the compounds. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.5.730
更新日期:1979-05-01 00:00:00
abstract::Preliminary studies showed that roxithromycin possessed significant in vitro activity against a variety of atypical mycobacteria such as the Mycobacterium avium complex, M. scrofulaceum, M. szulgai, M. malmoense, M. xenopi, M. marinum, and M. kansasii and rare pathogens such as M. chelonae and M. fortuitum. In this in...
journal_title:Antimicrobial agents and chemotherapy
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abstract::Intraoperative biliary cefamandole concentrations were determined in 16 patients with hepatobiliary pathology. These included seven patients with cholelithiasis, five with acute cholecystitis, two with recurrent ascending cholangitis, and two with liver abscesses. Bile collected 0.5 to 2.5 h after the last antibiotic ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.6.1087
更新日期:1982-12-01 00:00:00
abstract::Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infections, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk but might increase the risks of renal or liver toxicity or Clostridium diffici...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01838-17
更新日期:2018-02-23 00:00:00
abstract::The release of inflammatory bacterial products, such as lipopolysaccharide (LPS)/endotoxin, may be increased upon the administration of antibiotics. An improved quantitative understanding of endotoxin release and its relation to antibiotic exposure and bacterial growth/killing may be gained by an integrated analysis o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02070-19
更新日期:2020-03-24 00:00:00
abstract::In vivo treatment of susceptible Escherichia coli cultures with low concentrations of dihydrostreptomycin leads to a decline in polysomes and a corresponding increase in 70S particles which behave as run-off ribosomes, as well as free 30S and 50S subunits. We have examined the timing and extent of these effects on rib...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.3.341
更新日期:1975-03-01 00:00:00
abstract::This work investigated the molecular events driving the evolution of the CTX-M-type β-lactamases by the use of DNA shuffling of fragments of the blaCTX-M-14 and blaCTX-M-15 genes. Analysis of a total of 51 hybrid enzymes showed that enzymatic activity could be maintained in most cases, yet hybrids that were active pos...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00891-17
更新日期:2017-11-22 00:00:00
abstract::Cyclic phosphate derivative of DHPG, 2'-nor-cGMP [9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]-guani ne phosphate-oxide] was evaluated for activity against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo cells and in guinea pigs. By virus yield reduction and plaque reduction assays,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1563
更新日期:1989-09-01 00:00:00
abstract::We previously reported the isolation of a laboratory-derived Staphylococcus aureus mutant, 523k, that has constitutive low-level resistance to vancomycin (MIC = 5 micrograms/ml) and teicoplanin (MIC = 5 micrograms/ml) and elaborates a ca. 39-kDa cytoplasmic protein that was not detected in the parent strain 523 (MIC =...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.1.166
更新日期:1996-01-01 00:00:00
abstract::The need for daily parenteral administration is an important limitation in the clinical use of pentavalent antimonial drugs against leishmaniasis. In this study, amphiphilic antimony(V) complexes were prepared from alkylmethylglucamides (L8 and L10, with carbon chain lengths of 8 and 10, respectively), and their poten...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00639-13
更新日期:2013-09-01 00:00:00
abstract::An ampicillin-sulbactam combination was compared with ampicillin alone, chloramphenicol, clindamycin, and metronidazole against 272 strains of anaerobic bacteria. Chloramphenicol and ampicillin-sulbactam were the most effective, inhibiting 98 to 99% of strains tested at breakpoint (16 micrograms/ml). The combination o...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2012-09-01 00:00:00
abstract::Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezo...
journal_title:Antimicrobial agents and chemotherapy
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abstract::The in vitro activities of luliconazole, amorolfine, ciclopirox, and terbinafine were determined against 320 dermatophyte isolates from large toenails of onychomycosis patients enrolled into an ongoing phase 2b/3 clinical study. The geometric mean MIC for luliconazole was 0.00022 μg/ml against all isolates, compared t...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2014-06-01 00:00:00
abstract::Arylimidamides (AIAs) have been shown to have considerable biological activity against intracellular pathogens, includingTrypanosoma cruzi, which causes Chagas disease. In the present study, the activities of 12 novel bis-AIAs and 2 mono-AIAs against different strains ofT. cruziin vitroandin vivowere analyzed. The mos...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats. Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula. Clarithromycin was marginally superior to clindamycin against sm...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:1996-03-01 00:00:00
abstract::The antibiotic cerulenin markedly inhibits the growth of Escherichia coli. The effects of the antibiotic on cellular syntheses were studied by measuring the incorporation of labeled precursors into lipids and macromolecules. During the first 40 min after the addition of cerulenin to a culture of growing cells, lipid s...
journal_title:Antimicrobial agents and chemotherapy
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abstract::Ampicillin-resistant Enterococcus faecium (ARE) and vancomycin-resistant E. faecium (VRE) are important nosocomial pathogens. We quantified effects of probiotics and antibiotics on intestinal acquisition of ARE colonization in patients hospitalized in two non-intensive care unit (non-ICU) wards with high ARE prevalenc...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2010-07-01 00:00:00
abstract::Plasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2014-12-01 00:00:00
abstract::A vancomycin-resistant Staphylococcus aureus (VRSA) isolate was obtained from a patient in Pennsylvania in September 2002. Species identification was confirmed by standard biochemical tests and analysis of 16S ribosomal DNA, gyrA, and gyrB sequences; all of the results were consistent with the S. aureus identification...
journal_title:Antimicrobial agents and chemotherapy
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