Abstract:
:Dihydroorotate dehydrogenase (DHOD) is a pyrimidine biosynthetic enzyme which is usually directly linked to the mitochondrial respiratory chain. Antimalarial naphthoquinones such as atovaquone (566c80) inhibit malarial DHOD by inhibiting electron transport. Since atovaquone also has therapeutic activity against Pneumocystis carinii, the P. carinii DHOD may also be an important drug target. Organisms were obtained from immunosuppressed rats, incubated for 24 h in a short-term in vitro culture system, and then lysed. P. carinii lysates catalyzed the generation of orotate from dihydroorotate at a rate of 852 pmol/mg of protein per min. Control preparations made from uninfected mice showed much less total enzymatic activity and enzyme specific activity. As expected, P. carinii DHOD activity was susceptible to respiratory inhibitors such as cyanide, antimycin A, and salicylhydroxamic acid (SHAM). Susceptibility to SHAM suggests the presence of an alternative oxidase. In contrast, neither pentamidine nor 5-hydroxy-6-demethylprimaquine (5H6DP), a quinone metabolite of primaquine, inhibited the enzyme. Atovaquone inhibited DHOD by 76.3% at 100 microM and 36.5% at 10 microM. A similar degree of inhibition was found when the organisms were preincubated with the drug. Atovaquone inhibited P. carinii growth in vitro at a somewhat lower concentration (between 0.3 and 3 microM). In contrast, Plasmodium falciparum growth and enzyme activity are susceptible to nanomolar concentrations of atovaquone. Thus, while it is possible that atovaquone acts by inhibiting the P. carinii electron transport chain, the possibility of another drug target cannot be excluded.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Ittarat I,Asawamahasakda W,Bartlett MS,Smith JW,Meshnick SRdoi
10.1128/aac.39.2.325subject
Has Abstractpub_date
1995-02-01 00:00:00pages
325-8issue
2eissn
0066-4804issn
1098-6596journal_volume
39pub_type
杂志文章abstract::The effect of the cephalosporin precursors and amino acids of the aspartic acid family on antibiotic production by Streptomyces clavuligerus was investigated DL-meso-Diaminopimelate and L-lysine each stimulated specific antibiotic production by 75%. A fourfold increase in specific production was obtained by simultaneo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.1.74
更新日期:1982-01-01 00:00:00
abstract::This work in conjunction with the results presented in an earlier report (M. A. Purdy and K. L. Yielding, Antimicrob. Agents Chemother. 10:182--184, 1976) showed the following. (i) Nalidixic acid and novobiocin could inhibit post-ultraviolet and post-X-ray survival, implicating gyrase function in deoxyribonucleic acid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.16.3.247
更新日期:1979-09-01 00:00:00
abstract::Previous studies on tetracycline transport into Staphylococcus aureus identified a high-affinity, saturable uptake system for the antibiotic (Km, 4.76 microM) (B.L. Hutchings, Biochim. Biophys. Acta 174:734-738, 1969). However, the earlier results could not be confirmed using conditions that permitted energy-dependent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.12.2643
更新日期:1991-12-01 00:00:00
abstract::Emtricitabine [(-)FTC] [(-)-beta-2', 3'-dideoxy-5-fluoro-3'-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (-)FTC against WHV rep...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1757-1760.2000
更新日期:2000-06-01 00:00:00
abstract::Fungal infections, especially infections caused by Candida albicans, remain a challenging problem in clinical settings. Despite the development of more-effective antifungal drugs, their application is limited for various reasons. Thus, alternative treatments with drugs aimed at novel targets in C. albicans are needed....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
doi:10.1128/AAC.00726-15
更新日期:2015-10-01 00:00:00
abstract::Viral entry inhibitors represent an emerging mode of therapy for human immunodeficiency virus type 1 (HIV-1) infection. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. PRO 542 binds to the viral surface glycoprotein gp120 and blocks at...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.48.2.423-429.2004
更新日期:2004-02-01 00:00:00
abstract::The clinical vancomycin-intermediate Staphylococcus aureus (VISA) strain Mu50 carries two mutations in the vraSR and graRS two-component regulatory systems (TCRSs), namely, vraS(I5N) and graR(N197S) (hereinafter designated graR). The clinical heterogeneously vancomycin-intermediate S. aureus (hVISA) strain Mu3 shares ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00398-11
更新日期:2011-09-01 00:00:00
abstract::To compare the effect of ritonavir on plasma amprenavir pharmacokinetics, healthy adults received either fosamprenavir (700 mg twice a day [BID]) or amprenavir (600 mg BID) alone and in combination with ritonavir (100 mg BID). Ritonavir increased plasma amprenavir pharmacokinetic parameters to a similar extent when co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.50.4.1578-1580.2006
更新日期:2006-04-01 00:00:00
abstract::Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) inhibited herpes simplex virus type 1 (HSV-1) replication, although HSV-1 DNA was synthesized at normal levels in Vero cells. Viral capsids and extracellular virions were inhibited, and HSV-1 protein synthesis decreased by 50%, although no specific HSV-1 protein faile...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.5.941
更新日期:1986-05-01 00:00:00
abstract::The gram-positive bacterium Staphylococcus epidermidis is the most common cause of infections associated with catheters and other indwelling medical devices. S. epidermidis produces an extracellular slime that enables it to form adherent biofilms on plastic surfaces. We found that a biofilm-releasing enzyme produced b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.7.2633-2636.2004
更新日期:2004-07-01 00:00:00
abstract::Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain Enterobacteriaceae that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against ce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.6.792
更新日期:1979-06-01 00:00:00
abstract::More than 10(6) compounds were evaluated in a human immunodeficiency virus type 1 (HIV-1) high-throughput antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (UK-201844). UK-201844 exhibited antiviral activity against HIV-1 NL4-3 in MT-2 and PM1 cells, with 50% effective concentrations of 1.3 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00643-07
更新日期:2007-10-01 00:00:00
abstract::Malaria and trypanosomiasis are diseases which afflict millions and for which novel therapies are urgently required. We have tested two well-characterized cell-penetrating peptides (CPPs) for antiparasitic activity. One CPP, designated TP10, has broad-spectrum antiparasitic activity against Plasmodium falciparum, both...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01450-07
更新日期:2008-09-01 00:00:00
abstract::FCE 22891 is the oral prodrug of FCE 22101, a new broad-spectrum penem. The pharmacokinetics of FCE 22891 after single-dose administration, its absolute bioavailability, and the effect of food intake on its absorption were investigated in three different randomized crossover studies in healthy volunteers. Drug levels ...
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.34.6.1001
更新日期:1990-06-01 00:00:00
abstract::Ampicillin resistance in Enterococcus faecium is a serious concern worldwide, complicating the treatment of E. faecium infections. Penicillin-binding protein 5 (PBP5) is considered the main ampicillin resistance determinant in E. faecium The three known E. faecium clades showed sequence variations in the pbp5 gene tha...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02034-16
更新日期:2016-12-27 00:00:00
abstract::The in vitro activities of ceftaroline and comparators, using broth microdilution, were determined against 1,066 Staphylococcus aureus isolates from hospitalized patients. Seventeen medical centers from Latin American countries contributed isolates. Methicillin-resistant S. aureus (MRSA) percentages ranged from 46% (B...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.01833-15
更新日期:2015-12-01 00:00:00
abstract::Two carbapenem-resistant isolates, one Escherichia coli isolate and one Klebsiella pneumoniae isolate, recovered from an Algerian patient expressed a novel VIM-type metallo-beta-lactamase (MBL). The identified bla(VIM-19) gene was located on a ca. 160-kb plasmid and located inside a class 1 integron in both isolates. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00458-09
更新日期:2010-01-01 00:00:00
abstract::The continued evolution of bacterial resistance to the β-lactam class of antibiotics has necessitated countermeasures to ensure continued effectiveness in the treatment of infections caused by bacterial pathogens. One relatively successful approach has been the development of new β-lactam analogs with advantages over ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02240-19
更新日期:2020-07-22 00:00:00
abstract::In vitro interactions of ciprofloxacin with imipenem and amikacin were evaluated by the killing-curve technique against 26 Pseudomonas aeruginosa strains resistant to amikacin and resistant or moderately susceptible to ciprofloxacin and imipenem. Imipenem enhanced killing by ciprofloxacin in tests with 11 strains, whe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.6.959
更新日期:1987-06-01 00:00:00
abstract::MarA47(Yp) from Yersinia pestis, showing 47% identity to Escherichia coli MarA in its N terminus, caused resistance to antibiotics and to organic solvents when expressed in both E. coli and Y. pestis. Resistance was linked to increased expression of the AcrAB multidrug efflux pump. In four of five spontaneous multidru...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00015-06
更新日期:2006-09-01 00:00:00
abstract::VT-1161 and VT-1598 are promising investigational tetrazole antifungals that have shown in vitro and in vivo activity against Candida and other fungi. Candida glabrata is a problematic opportunistic pathogen that is associated with high mortality in invasive infection, as well as both intrinsic and rapidly acquired an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01304-19
更新日期:2019-09-23 00:00:00
abstract::A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weig...
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.41.6.1256
更新日期:1997-06-01 00:00:00
abstract::The in vitro activities of two investigational quinolones, sparfloxacin (previously designated AT 4140) and PD 127391, were determined for 30 strains each of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum and compared with those of ciprofloxacin, tetracycline, clindamycin, and erythromycin. Eryt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.6.1181
更新日期:1991-06-01 00:00:00
abstract::Viral pathogens causing global disease burdens are often characterized by high rates of evolutionary changes. The extensive viral diversity at baseline can shorten the time to escape from therapeutic or immune selective pressure and alter mutational pathways. The impact of genotypic background on the barrier to resist...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00539-19
更新日期:2019-07-25 00:00:00
abstract::Isoniazid (INH) remains the most safe and cost-effective drug for the treatment and prophylaxis of tuberculosis. The use of INH has increased over the past years, largely as a result of the coepidemic of human immunodeficiency virus infection. It is frequently given chronically to critically ill patients who are copre...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.2.382-392.2001
更新日期:2001-02-01 00:00:00
abstract::Maribavir (1263W94, VP-41263) is an oral anticytomegalovirus agent under clinical development. The pharmacokinetics and safety of maribavir and the effects of maribavir on the activities of cytochrome P450 (CYP) 1A2, CYP 2C9, CYP 2C19, CYP 2D6, CYP 3A, N-acetyltransferase-2 (NAT-2), and xanthine oxidase (XO) were eval...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.50.4.1130-1135.2006
更新日期:2006-04-01 00:00:00
abstract::In Pseudomonas aeruginosa, the quorum-sensing (QS) system is closely related to biofilm formation. We previously demonstrated that 14-alpha-lipoyl andrographolide (AL-1) has synergistic effects on antibiofilm and antivirulence factors (pyocyanin and exopolysaccharide) of P. aeruginosa when combined with conventional a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01119-12
更新日期:2012-12-01 00:00:00
abstract::Placental drug transfer is important for achieving better pharmacotherapy in pregnant women and in fetuses. In the present study, we examined the effects of anti-hepatitis C virus (HCV) and anti-HIV drugs on organic anion transport in human placental BeWo cells. The cellular uptake of two fluorescence organic anions, ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01634-15
更新日期:2015-12-01 00:00:00
abstract::The pharmacokinetics and therapeutic efficacy of gentamicin were investigated in an experimental pleural empyema rabbit model. Pleural effusion was induced by the intrapleural administration of turpentine, and empyema was induced by direct inoculation of the effusion with Klebsiella pneumoniae. Pleural empyema compare...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.7.982
更新日期:1987-07-01 00:00:00
abstract::A collection of 2,278 isolates belonging to 86 different fungal species was tested with micafungin and eight other drugs using the EUCAST procedures. Micafungin was active against species of Candida and Aspergillus (even azole-resistant species) as well as Penicillium spp., Scedosporium apiospermum, and Acremonium spp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01543-08
更新日期:2009-05-01 00:00:00