Abstract:
:Approximately 150,000 small-molecule compounds were tested by a robotic screening assay for their ability to inhibit nucleoside triphosphate hydrolase (NTPase), a novel enzyme of the tachyzoite form of Toxoplasma gondii. Five unrelated species of compounds were found to inhibit the activities of both NTPase isoforms (NTPase isoform I [NTPase-I] and NTPase-II). The 50% inhibitory concentrations (IC(50)s) ranged from 0.1 to 20 microM, and in general, the IC(50)s were similar for both NTPase isoforms. However, the activity of NTPase-I was 20 times more sensitive than the activity of NTPase-II to one of the inhibitors: 9-hydroxy-10-(pentachlorophenoxy)stearic acid. The five compounds identified also prevented tachyzoite replication in vitro, with IC(50)s ranging from approximately 7 to > or =50 microM. The most effective of these initial compounds, 2-phenylthio-indole, was used to identify six additional, structurally related compounds, which were tested for their inhibitory effects on enzyme activities and tachyzoite replication. Surprisingly, these compounds were competitive inhibitors of NTPase-I but noncompetitive inhibitors of NTPase-II. Modifications to the indole and phenol rings resulted in alterations of activity, thus providing insight into the structural features that are important for inhibition of T. gondii NTPases.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Asai T,Takeuchi T,Diffenderfer J,Sibley LDdoi
10.1128/aac.46.8.2393-2399.2002subject
Has Abstractpub_date
2002-08-01 00:00:00pages
2393-9issue
8eissn
0066-4804issn
1098-6596journal_volume
46pub_type
杂志文章abstract::The Burkholderia cepacia complex (BCC) is a group of bacterial pathogens that are highly antibiotic resistant and associated with debilitating respiratory infections. Although bacteriophages of the BCC have been isolated and characterized, no studies have yet examined phage therapy against the BCC in vivo. In a caterp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01166-08
更新日期:2009-05-01 00:00:00
abstract::We present a 31-year-old female who had undergone an allogeneic bone marrow transplantation and who was started on intravenous posaconazole for pulmonary mycosis while undergoing continuous venovenous hemofiltration (CVVH). We performed steady-state pharmacokinetic evaluations for both posaconazole and sulfobutylether...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01493-15
更新日期:2015-10-01 00:00:00
abstract::3-Deazauridine, a synthetic analogue of uridine and a potential antitumor agent, was found to possess antiviral activity against a number of ribonucleic acid-containing animal viruses in mammalian cell culture. Inhibition of virus-induced cytopathogenic effects by 3-deazauridine was observed in cells infected with rhi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.2.3.159
更新日期:1972-09-01 00:00:00
abstract::An experiment was conducted in animal facilities to compare the impacts of four avian colibacillosis treatments-oxytetracycline (OTC), trimethoprim-sulfadimethoxine (SXT), amoxicillin (AMX), or enrofloxacin (ENR)-on the susceptibility of Escherichia coli in broiler intestinal tracts. Birds were first orally inoculated...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05617-11
更新日期:2012-01-01 00:00:00
abstract::Subinhibitory concentrations of antibiotics have been shown to enhance biofilm formation in multiple bacterial species. While antibiotic exposure has been associated with modulated expression of many biofilm-related genes, the mechanisms of drug-induced biofilm formation remain a focus of ongoing research efforts and ...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2017-12-21 00:00:00
abstract::Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 microg/ml) and glycopept...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00510-07
更新日期:2008-07-01 00:00:00
abstract::N-Formimidoyl thienamycin (MK0787) was active against beta-lactamase-producing strains and was an effective inhibitor of beta-lactamases extracted and purified from these strains except for plasmid-mediated penicillinase type IV. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.5.837
更新日期:1980-11-01 00:00:00
abstract::GSQ1530 is a compound derived from a newly identified class of antibiotics referred to as heteroaromatic polycyclic (HARP) antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of GSQ1530. By using an NCCLS broth microdilution assay, the activities of GSQ1530 and other antibiotics were c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.10.3168-3174.2002
更新日期:2002-10-01 00:00:00
abstract::A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephal...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.2.273
更新日期:1980-02-01 00:00:00
abstract::BO-1341, a new antipseudomonal semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefotaxime, and cefoperazone. The in vitro activity of BO-1341 was generally superior or comparable to the activities of the reference antibiotics against clinical...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1423
更新日期:1989-09-01 00:00:00
abstract::The disposition of cefonicid (2 g intravenously every 24 h) was assessed in 15 patients with skin and skin structure infections. Trough and peak concentrations in serum were measured on two successive days to verify the attainment of steady state; and 1 trough and 12 postdose values of the concentration in serum were ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.4.485
更新日期:1988-04-01 00:00:00
abstract::The 2-amino-5-halo-pyrimidinones, which are potent interferon inducers and antiviral agents, were found to be protective against lethal cytomegalovirus (CMV) challenge in weanling or neonatal mice when administered before virus challenge. This protection was dependent upon the dosage of pyrimidinone administered. Wean...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.4.485
更新日期:1985-10-01 00:00:00
abstract::Five R plasmids transferred from Asian strains of Vibrio cholerae all proved to be members of compatibility group C. A non-self-transmissible plasmid, stable in V. cholerae, was mobilized for transfer to Escherichia coli K-12 and found to be unstably inherited in that host. Plasmids of group C and P transferred to a w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.4.585
更新日期:1977-04-01 00:00:00
abstract::A sensitive and specific high-pressure liquid chromatographic method is described for the determination of the antibacterial drug flumequine and a major metabolite, 7-hydroxyflumequine, in human plasma and urine. The assay was linear over a concentration range of 1 to 120 micrograms/ml for both compounds. This method ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.3.301
更新日期:1984-03-01 00:00:00
abstract::Small unilamellar amphotericin B liposomes can reduce the toxicity of amphotericin B. In this study, we compared the physical, antifungal, pharmocokinetic, and toxic properties of two liposomal amphotericin B products, AmBisome and Anfogen, that have the same chemical composition but are manufactured differently. In v...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00870-07
更新日期:2008-01-01 00:00:00
abstract::Many potent antiviral drugs have been developed against HIV-1, and their combined action is usually successful in achieving durable virus suppression in infected individuals. This success is based on two effects: additive or even synergistic virus inhibition and an increase in the genetic threshold for development of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01486-17
更新日期:2017-11-22 00:00:00
abstract::Triple antifungal combinations are used against refractory invasive aspergillosis without an adequate understanding of their pharmacodynamic interactions. We initially studied the in vitro triple combination of voriconazole, amphotericin B, and caspofungin against Aspergillus fumigatus, A. flavus, and A. terreus by a ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00873-06
更新日期:2007-06-01 00:00:00
abstract::Wild-type Proteus strains are usually resistant to colistin. We have observed an increase in the level of colistin resistance in four clinical isolates of P. vulgaris, P. morganii, and P. rettgeri by prior treatment with subinhibitory concentrations of the drug. The enhanced resistance in these strains was lost after ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.12.1.1
更新日期:1977-07-01 00:00:00
abstract::Vaborbactam (formerly RPX7009) is a member of a new class of β-lactamase inhibitor with pharmacokinetic properties similar to those of many β-lactams, including carbapenems. The pharmacokinetics and safety of vaborbactam were evaluated in 80 healthy adult subjects in a first-in-human randomized, placebo-controlled, do...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.00568-16
更新日期:2016-09-23 00:00:00
abstract::The in vitro activity of gentamicin was compared with its therapeutic efficacy in rabbits with Streptococcus faecalis endocarditis. The test strain was resistant to gentamicin as measured by MICs and MBCs determined in Mueller-Hinton broth alone or in broth supplemented with 50% rabbit serum. Gentamicin also failed to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.2.224
更新日期:1985-02-01 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
doi:10.1128/AAC.01667-15
更新日期:2016-03-25 00:00:00
abstract::The spread of antibiotic-resistant bacteria presents a global health challenge. Efficient surveillance of bacteria harboring antibiotic resistance genes (ARGs) is a critical aspect to controlling the spread. Increased access to microbial genomic data from many diverse populations informs this surveillance but only whe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00867-20
更新日期:2020-10-20 00:00:00
abstract::HMR 3647 (telithromycin), a new ketolide, is active on intracellular pathogens. It was previously demonstrated that it inhibits superoxide anion production in a time- and concentration-dependent manner, at concentrations which inhibit 50% of the control response of about 55 microg/ml (5 min) to 30 microg/ml (30 min); ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.5.1364-1374.2002
更新日期:2002-05-01 00:00:00
abstract::The aim of this study was to reveal population pharmacokinetics and assess the efficacies of various dosage regimens of sulbactam in terms of the probability of target attainment with this agent over a range of MICs. Monte Carlo simulations were performed to determine the probability of attaining specific pharmacodyna...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00342-13
更新日期:2013-07-01 00:00:00
abstract::Fifty volunteers randomly assigned to one of five hand washing agents (10 subjects per agent)--a nonantiseptic liquid soap (control), an antiseptic hand rinse containing 60% isopropyl alcohol (IPA) with emollients (Alc A), an antiseptic hand rinse containing 70% IPA and 0.5% chlorhexidine gluconate with emollients (Al...
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.30.4.542
更新日期:1986-10-01 00:00:00
abstract::The biosynthetic gene cluster of the aminocoumarin antibiotic coumermycin A(1) was cloned by screening of a cosmid library of Streptomyces rishiriensis DSM 40489 with heterologous probes from a dTDP-glucose 4,6-dehydratase gene, involved in deoxysugar biosynthesis, and from the aminocoumarin resistance gyrase gene gyr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.11.3040-3048.2000
更新日期:2000-11-01 00:00:00
abstract::We investigated the antistaphylococcal activity of daptomycin, vancomycin, oxacillin, gentamicin, and rifampin in human monocyte-derived macrophages. Compared with vancomycin and oxacillin, daptomycin had the most rapid and greatest antibacterial activity, but that of oxacillin was most sustained. The combination of d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00973-06
更新日期:2007-04-01 00:00:00
abstract::Clinical isolates of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum beta-lactamases or plasmid-mediated AmpC beta-lactamases were screened for qnrA and qnrB genes. QnrB was present in 54 of 54 DHA-1-producing K. pneumoniae isolates and 10 of 45 SHV-12-producing ones, suggesting that the distrib...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00841-06
更新日期:2007-01-01 00:00:00
abstract::The in vitro activities of the new triazole, ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of Cryptococcus neoformans. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.10.2883-2886.2000
更新日期:2000-10-01 00:00:00
abstract::Using a new rabbit model of methicillin-susceptible Staphylococcus aureus knee prosthesis infection, we compared the efficacies of sparfloxacin (50 mg/kg of body weight subcutaneously, twice a day) and pefloxacin (50 mg/kg subcutaneously, twice a day). A partial knee replacement was performed with a silicone implant f...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.2111
更新日期:1996-09-01 00:00:00