Abstract:
:Dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a well-validated antifolate drug target in certain pathogenic apicomplexans, but not in the genus Babesia, including Babesia gibsoni. Therefore, we isolated, cloned, and expressed the wild-type B. gibsoni dhfr-ts gene in Escherichia coli and evaluated the inhibitory effect of antifolates on its enzyme activity, as well as on in vitro parasite growth. The full-length gene consists of a 1,548-bp open reading frame encoding a 58.8-kDa translated peptide containing DHFR and TS domains linked together in a single polypeptide chain. Each domain contained active-site amino acid residues responsible for the enzymatic activity. The expressed soluble recombinant DHFR-TS protein was approximately 57 kDa after glutathione S-transferase (GST) cleavage, similar to an approximately 58-kDa native enzyme identified from the parasite merozoite. The non-GST fusion recombinant DHFR enzyme revealed K(m) values of 4.70 +/- 0.059 (mean +/- standard error of the mean) and 9.75 +/- 1.64 microM for dihydrofolic acid (DHF) and NADPH, respectively. Methotrexate was a more-potent inhibitor of the enzymatic activity (50% inhibition concentration [IC(50)] = 68.6 +/- 5.20 nM) than pyrimethamine (IC(50) = 55.0 +/- 2.08 microM) and trimethoprim (IC(50) = 50 +/- 12.5 microM). Moreover, the antifolates' inhibitory effects on DHFR enzyme activity paralleled their inhibition of the parasite growth in vitro, indicating that the B. gibsoni DHFR could be a model for studying antifolate compounds as potential drug candidates. Therefore, the B. gibsoni DHFR-TS is a molecular antifolate drug target.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Aboge GO,Jia H,Terkawi MA,Goo YK,Nishikawa Y,Sunaga F,Namikawa K,Tsuji N,Igarashi I,Suzuki H,Fujisaki K,Xuan Xdoi
10.1128/AAC.00384-08subject
Has Abstractpub_date
2008-11-01 00:00:00pages
4072-80issue
11eissn
0066-4804issn
1098-6596pii
AAC.00384-08journal_volume
52pub_type
杂志文章abstract::SCY-078 is an orally active antifungal whose target is the β-(1,3)-d-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078-resistant Candida glabrata isolates following drug exposure in vitro Resistant isolates were analyzed using broth microdilution methodology and FKS sequencing. The kinetic inhibi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00833-17
更新日期:2017-08-24 00:00:00
abstract::Cefoxitin resistance, but not resistance to clindamycin, erythromycin, lincomycin, or tetracycline, was transferred by a conjugation-like process from Bacteroides thetaiotaomicron UN101, a clinical isolate haboring four kinds of plasmids, to other Bacteroides species. Of a sample of 20 cefoxitin-resistant transconjuga...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.4.701
更新日期:1982-10-01 00:00:00
abstract::A Staphylococcus aureus surveillance program was initiated in the United States to examine the in vitro activity of ceftaroline and epidemiologic trends. Susceptibility testing by Clinical and Laboratory Standards Institute broth microdilution was performed on 4,210 clinically significant isolates collected in 2009 fr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00315-11
更新日期:2011-09-01 00:00:00
abstract::Mupirocin is a topical antimicrobial used to decolonize patients who carry methicillin-resistant Staphylococcus aureus (MRSA), and the topical agent retapamulin may be a potential alternative therapy. The goal of this study was to determine the in vitro activity of retapamulin as well as a panel of 15 antimicrobial ag...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01568-15
更新日期:2015-12-14 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::No studies have investigated whether discontinuation of ethambutol (EMB) based on the susceptibility to isoniazid and rifampin as determined by the GenoType MTBDRplus assay would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of intensive phase treatment based on the result o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00980-19
更新日期:2019-09-16 00:00:00
abstract::The ampD gene product regulates the expression of AmpC beta-lactamase in gram-negative bacteria and is proposed to be involved in peptidoglycan metabolism. In this study, we sequenced the ampD wild type and three mutant genes of Enterobacter cloacae and Citrobacter freundii. They exhibited a high degree of homology wi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.2.224
更新日期:1993-02-01 00:00:00
abstract::A single-nucleotide polymorphism-based cluster grouping (SCG) classification system for Mycobacterium tuberculosis was used to examine antibiotic resistance type and resistance mutations in relationship to specific evolutionary lineages. Drug resistance and resistance mutations were seen across all SCGs. SCG-2 had hig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00619-07
更新日期:2007-11-01 00:00:00
abstract::Rifampin was shown in vitro to decrease the amphotericin B minimal inhibitory concentrations of all of 10 strains of Coccidioides immitis tested. These decreases ranged from two- to fourfold and occurred with rifampin concentrations of 10 to 40 mug/ml. Rifampin alone was without effect. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.6.783
更新日期:1974-12-01 00:00:00
abstract::C-8-methoxy fluoroquinolones were more lethal than C-8-bromine, C-8-ethoxy, and C-8-H derivatives for Staphylococcus aureus, especially when topoisomerase IV was resistant. The methoxy group also increased lethality against wild-type cells when protein synthesis was inhibited. These properties encourage refinement of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.4.956
更新日期:1998-04-01 00:00:00
abstract::Alpha interferon and ribavirin are required in combination to achieve a sustained virological response in the treatment of hepatitis C virus (HCV) infection. Alpha interferon has direct antiviral activity and also enhances HCV-specific T-cell responses. Ribavirin has little direct activity against HCV but reduces hepa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3382-3389.2004
更新日期:2004-09-01 00:00:00
abstract::Oseltamivir is the most widely used anti-influenza drug. In the 2009 H1N1 pandemic, in which the influenza viruses were oseltamivir sensitive, obesity was identified as a risk factor for severe disease and unfavorable outcomes. The aim of this study was to investigate the pharmacokinetic properties of oseltamivir and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01786-13
更新日期:2014-01-01 00:00:00
abstract::The resistome of P. aeruginosa for three β-lactam antibiotics, namely, ceftazidime, imipenem, and meropenem, was deciphered by screening a comprehensive PA14 mutant library for mutants with increased or reduced susceptibility to these antimicrobials. Confirmation of the phenotypes of all selected mutants was performed...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00257-10
更新日期:2010-10-01 00:00:00
abstract::Sulfobutylether-beta-cyclodextrin (SBECD), a large cyclic oligosaccharide that is used to solubilize voriconazole (VRC) for intravenous administration, is eliminated mainly by renal excretion. The pharmacokinetics of SBECD and voriconazole in patients undergoing extracorporeal renal replacement therapies are not well ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01540-09
更新日期:2010-06-01 00:00:00
abstract::The antifungal activities of amphotericin B and two triazoles, Sch 39304 and fluconazole, were tested against Histoplasma capsulatum. In this study Sch 39304 compared favorably with amphotericin B in treating histoplasmosis in normal and leukopenic mice, whereas fluconazole was much less active. The differences in the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.4.524
更新日期:1990-04-01 00:00:00
abstract::Whole and fractionated latex of Asclepias syriaca was tested for antimicrobial or growth-promoting activity with 16 genera and species of bacteria. Latex and extracted fractions (distilled water, acetic acid, sodium bicarbonate, sulfuric acid, and ethyl ether) possessed no detectable antimicrobial activity. Comparison...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.2.247
更新日期:1973-02-01 00:00:00
abstract::GS-9148 is an investigational phosphonate nucleotide analogue inhibitor of reverse transcriptase (RT) (NtRTI) of human immunodeficiency virus type 1 (HIV-1). This compound is an adenosine derivative with a 2',3'-dihydrofuran ring structure that contains a 2'-fluoro group. The resistance profile of GS-9148 is unique in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01738-10
更新日期:2011-06-01 00:00:00
abstract::A potential strategy that can be used to combat the worldwide AIDS epidemic is the development of a vaginal microbicide that prevents the sexual transmission of human immunodeficiency virus type 1 (HIV-1). Certain CC chemokines, including RANTES, MIP-1alpha, and MIP-1beta, might facilitate the development of such micr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.4.1497-1509.2006
更新日期:2006-04-01 00:00:00
abstract::The pyrazinamide (PZA) analog 5-chloropyrazinamide (5-Cl PZA) is active against mycobacterial species, including PZA-resistant strains of Mycobacterium tuberculosis. In M. smegmatis, overexpression of the type 1 fatty acid synthase (FAS I) confers resistance to 5-Cl PZA, a potent FAS I inhibitor. Since M. tuberculosis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00529-10
更新日期:2010-12-01 00:00:00
abstract::A series of twelve recently synthesized 6-substituted derivatives of 9-beta-d-ribofuranosylpurine 3',5'-cyclic phosphate (RPcMP) were evaluated for in vitro antiviral activity, using inhibition of viral cytopathogenic effect as the primary parameter for evaluation. Inhibition of the development of intra- and extracell...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.6.652
更新日期:1974-06-01 00:00:00
abstract::Coresistance to human reserve antibiotics can be selected by antibiotics used in veterinary medicine. A Clostridium perfringens strain isolated from pig manure was resistant to the reserve drug linezolid and, simultaneously, resistant against florfenicol and erythromycin. We detected a new mutation in a highly conserv...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01208-09
更新日期:2010-03-01 00:00:00
abstract::Sixteen weeks of treatment with clarithromycin (CLARI) alone displayed significant bactericidal activity against Mycobacterium avium complex infection in beige mice. Only two combined regimens, CLARI combined with an initial 4 or 8 weeks of amikacin (AMIKA), displayed activity greater than that displayed by CLARI alon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.3.608
更新日期:1995-03-01 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::Minocycline and valproic acid are potential adjuvant therapies for the treatment of human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine whether minocycline alone or in combination with valproic acid affected atazanavir plasma concentrations. Twelve adult HIV-i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00194-08
更新日期:2008-09-01 00:00:00
abstract::Since the discovery and use of penicillin, the increase of antibiotic resistance among bacterial pathogens has become a major health concern. The most prevalent resistance mechanism in Gram-negative bacteria is due to β-lactamase expression. Class D β-lactamases are of particular importance due to their presence in mu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01483-13
更新日期:2014-01-01 00:00:00
abstract::Combination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only a few other combinations are now available. Increasing concern regarding the emergence and spread of artemisinin resistance in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02307-19
更新日期:2020-10-20 00:00:00
abstract::Since transmission of Chagas' disease by the insect vector is under control in Brazil, transmission by blood transfusion is acquiring special relevance in areas where the disease is endemic and also in countries whose populations are free of infection but that are receiving immigrants from areas where the disease is e...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.3.613
更新日期:1996-03-01 00:00:00
abstract::Mycobacterium tuberculosis and the fast-growing species Mycobacterium abscessus are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant M. tuberculosis strains and the high level of intrinsic resistance of M....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01696-17
更新日期:2018-04-26 00:00:00
abstract::We report two cases of daptomycin (DAP)-nonsusceptible (DNS) vancomycin-intermediate Staphylococcus aureus (VISA) vertebral osteomyelitis cases complicated by bacteremia treated with high-dose daptomycin and trimethoprim-sulfamethoxazole. Both patients responded rapidly and favorably to this combination. The clinical ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01046-12
更新日期:2012-11-01 00:00:00
abstract::The effects of free amphotericin B (as Fungizone) and amphotericin B (AMB) incorporated into liposomes on the proliferation of lymphocytes were determined. Freshly obtained guinea pig and rat antigen-specific lymphocytes were compared with rat T-lymphocyte cell lines cultured for a long period of time. Incorporation o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.5.879
更新日期:1991-05-01 00:00:00