Abstract:
:The antiviral activity of a new series of thymidine analogs was determined against vaccinia virus (VV), cowpox virus (CV), herpes simplex virus, and varicella-zoster virus. Several compounds were identified that had good activity against each of the viruses, including a set of novel 5-substituted deoxyuridine analogs. To investigate the possibility that these drugs might be phosphorylated preferentially by the viral thymidine kinase (TK) homologs, the antiviral activities of these compounds were also assessed using TK-deficient strains of some of these viruses. Some of these compounds were shown to be much less effective in the absence of a functional TK gene in CV, which was unexpected given the high degree of amino acid identity between this enzyme and its cellular homolog. This unanticipated result suggested that the CV TK was important in the mechanism of action of these compounds and also that it might phosphorylate a wider variety of substrates than other type II enzymes. To confirm these data, we expressed the VV TK and human TK1 in bacteria and isolated the purified enzymes. Enzymatic assays demonstrated that the viral TK could efficiently phosphorylate many of these compounds, whereas most of the compounds were very poor substrates for the cellular kinase, TK1. Thus, the specific phosphorylation of these compounds by the viral kinase may be sufficient to explain the TK dependence. This unexpected result suggests that selective phosphorylation by the viral kinase may be a promising new approach in the discovery of highly selective inhibitors of orthopoxvirus replication.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Prichard MN,Keith KA,Johnson MP,Harden EA,McBrayer A,Luo M,Qiu S,Chattopadhyay D,Fan X,Torrence PF,Kern ERdoi
10.1128/AAC.01447-06subject
Has Abstractpub_date
2007-05-01 00:00:00pages
1795-803issue
5eissn
0066-4804issn
1098-6596pii
AAC.01447-06journal_volume
51pub_type
杂志文章abstract::Tobramycin-resistant burn wound isolates of Klebsiella pneumoniae and Enterobacter cloacae, together with Escherichia coli K-12 transconjugants from these two strains, were examined for plasmid deoxyribonucleic acid (DNA). All the resistant strains contained a common, high-molecular-weight, covalently closed circular ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.2.312
更新日期:1978-02-01 00:00:00
abstract::The activity of four antifungal agents against 15 systemic (blood and vascular catheter) and 10 superficial (skin) Malassezia furfur isolates was evaluated. MIC ranges were similar for the two groups of organisms: amphotericin B, 0.3 to 2.5 micrograms/ml; flucytosine, greater than 100 micrograms/ml; miconazole, 0.4 to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.6.951
更新日期:1987-06-01 00:00:00
abstract::Patients with severe coccidioidomycosis infections are often treated with either amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB). Outcome data with these agents in severe coccidioidomycosis cases are currently lacking. The purpose of this study is to evaluate the efficacy and toxicity of ABLC a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02293-17
更新日期:2018-06-26 00:00:00
abstract::The anti-human immunodeficiency virus type I (anti-HIV-1) effects of gamma-glutamylcysteine ethyl ester (gamma-GCE; TEI-2306) were examined in vitro. In initial studies using a vigorously HIV-1-producing human T-lymphocytic cell line, gamma-GCE displayed a novel biphasic repressive effect on chronic HIV-1 infection th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.5.1200
更新日期:1998-05-01 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
pub_type: 杂志文章
doi:10.1128/aac.3.5.549
更新日期:1973-05-01 00:00:00
abstract::OXA-48-like carbapenemases have only recently emerged in Europe. OXA-162 is a rare OXA-48 variant usually coexpressed with extended-spectrum β-lactamases. Here, we report the identification of the first OXA-162 carbapenemase-producing Klebsiella pneumoniae isolates, which coexpressed an AmpC cephalosporinase (DHA-1), ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01514-15
更新日期:2015-12-14 00:00:00
abstract::The assembly of hepatitis B virus (HBV) core protein (HBc) into capsids represents a critical step of viral replication. HBc has multiple functions during the HBV life cycle, which makes it an attractive target for antiviral therapies. Capsid assembly modulators (CAMs) induce the formation of empty capsid or aberrant ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00835-18
更新日期:2018-09-24 00:00:00
abstract::Butylated hydroxytoluene (BHT) is a potent inactivator of the enveloped bacterial virus ø6 at concentrations as low as 3 x 10(-5) M. The viral envelope is not removed by BHT treatment, in contrast to the effects of exposure to the detergent Triton X-100. BHT-treated viruses are morphologically indistinguishable from c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.1.96
更新日期:1976-07-01 00:00:00
abstract::Defensins are small cationic bactericidal peptides present abundantly in the granules of polymorphonuclear neutrophils (PMNs). Human PMNs contain four defensins termed HNP-1 to HNP-4. We used a new assay system in agar plates, the radial diffusion assay, to evaluate the effects of human defensins against gram-positive...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.10.2280
更新日期:1996-10-01 00:00:00
abstract::Using an immunocompetent murine model of invasive aspergillosis (IA), we previously reported that the efficacy of liposomal amphotericin B (L-AmB) (Ambisome) is not hampered by the presence of azole resistance mutations in Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P. E. Verweij, Anti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02479-16
更新日期:2017-05-24 00:00:00
abstract::The bactericidal activity of clindamycin, chloramphenicol, and gentamicin alone and of gentamicin plus clindamycin and gentamicin plus chloramphenicol was studied on 8 strains of Escherichia coli and 10 strains of Bacteroides fragilis isolated from clinical material. Gentamicin did not interfere with the activity of c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.12.2.135
更新日期:1977-08-01 00:00:00
abstract::The activity of two cefoperazone-sulbactam combinations against anaerobic bacteria was tested and compared both with that of cefoperazone alone and with that of other commonly used antimicrobial agents. Imipenem was the most active of the tested agents, followed by chloramphenicol, metronidazole, and cefoperazone-sulb...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.3.403
更新日期:1988-03-01 00:00:00
abstract::Rifapentine is highly protein bound in blood, but the free, unbound drug is the microbiologically active fraction. In this exploratory study, we characterized the free plasma fraction of rifapentine in 41 patients with tuberculosis. We found a lower total rifapentine concentration but significantly higher free rifapen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01730-13
更新日期:2014-08-01 00:00:00
abstract::An Escherichia coli strain with a plasmidic amikacin resistance has been selected for which the evidence strongly indicates that resistance is mediated by aminoglycoside phosphotransferase [APH(3')-II]: (i) this resistance was coupled with resistance against kanamycin and neomycin; (ii) partially purified APH(3')-II[A...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.3.344
更新日期:1981-09-01 00:00:00
abstract::Primaquine is currently the only drug available for radical cure of Plasmodium vivax and P. ovale liver infection stages, but limited safety data exist for children <10 years of age. Detailed daily assessments of side effects in glucose-6-phosphate dehydrogenase (G6PD)-normal children treated with 14 days of primaquin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05566-11
更新日期:2012-04-01 00:00:00
abstract::A novel algorithm designed for the screening of carbapenemase-producing Enterobacteriaceae (CPE), based on faropenem and temocillin disks, was compared to that of the Committee of the Antibiogram of the French Society of Microbiology (CA-SFM), which is based on ticarcillin-clavulanate, imipenem, and temocillin disks. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00796-17
更新日期:2017-07-25 00:00:00
abstract::An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells we...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1116
更新日期:1996-05-01 00:00:00
abstract::Mycobacterium abscessus has emerged as an important pathogen in people with chronic inflammatory lung diseases such as cystic fibrosis, and recent reports suggest that it may be transmissible by fomites. M. abscessus exhibits two major colony morphology variants: a smooth morphotype (MaSm ) and a rough morphotype (MaR...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01782-17
更新日期:2018-02-23 00:00:00
abstract::The polymixin colistin represents a last resort antibiotic for multidrug resistant infections, but its use is limited by the frequent onset of acute drug-induced kidney injury (DIKI). It is essential to closely monitor kidney function prior to and during colistin treatment in order to pinpoint early signs of injury an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01650-19
更新日期:2019-10-07 00:00:00
abstract::In this study, we characterized two tigecycline-resistant Klebsiella pneumoniae isolates from dog urine samples. The isolates were genetically unrelated, belonging to sequence type 11 (ST11) and ST147, both classically related to human isolates. To the best of our knowledge, this is the first identification of tigecyc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02640-16
更新日期:2017-05-24 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::Nine carbapenem-resistant Enterobacteriaceae isolates collected from eight patients in five German hospitals were investigated. Six isolates produced the OXA-48 carbapenemase, and three isolates produced OXA-162, which is a point mutant form of OXA-48. Both carbapenemase genes were located on IncL/M-type conjugative p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05315-11
更新日期:2012-04-01 00:00:00
abstract::Two types of transmissible plasmids which encode resistance to trimethoprim-sulfamethoxazole were found among five animal isolates of Salmonella krefeld. This is the first report of plasmid-mediated resistance to trimethoprim-sulfamethoxazole in Salmonella strains isolated in the United States. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.3.495
更新日期:1983-03-01 00:00:00
abstract::An increase in the number of tuberculosis cases caused by multiple-drug-resistant strains of Mycobacterium tuberculosis has stimulated search for new antituberculous agents. Beta-lactam antibiotics, traditionally regarded as ineffective against tuberculosis, merit consideration. Four major penicillin-binding proteins ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.12.2620
更新日期:1995-12-01 00:00:00
abstract::Doxycycline is reported to impair second-generation parasite schizogony. The effects of doxycycline alone and combined with dihydroartemisinin were investigated in a murine malaria model. Doxycycline lowered the rate of parasite growth within 2 days, with maximum effect in 6 days. Addition of dihydroartemisinin led to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00529-07
更新日期:2007-12-01 00:00:00
abstract::Hydroxamate-based chelators of iron are potent inhibitors of in vitro growth of Plasmodium falciparum. Two types of such chelators, the natural desferrioxamine and the synthetic reversed siderophore RSFileum2, are prototypes of antimalarial agents whose action spectra differ in the speed of action, stage dependence, a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.61
更新日期:1995-01-01 00:00:00
abstract::Intranasal inoculation of newborn mice with Herpesvirus hominis (HVH) type 2 provides a model for disseminated herpesvirus infections of human newborn infants. Treatment of this experimental infection with polyinosinic-polycytidylic acid [poly(I:C)] significantly increased the mean survival time and markedly altered t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.6.793
更新日期:1975-06-01 00:00:00
abstract::Infection with multiple ganciclovir-resistant human cytomegalovirus mutants, containing different substitutions and deletions in the UL97 gene, was found in a patient with severe combined immunodeficiency (SCID) within 3 weeks of ganciclovir therapy. A novel 11-codon deletion at positions 590 to 600 was identified. Th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.2.593-595.2001
更新日期:2001-02-01 00:00:00
abstract::A plant pathogenic actinomycete identified as Streptomyces lydicus was isolated from the deep-pitted scab lesions of potato tubers. This strain produces a new polypeptide antibiotic named chandramycin. The antibiotic was isolated from culture broth by extraction with organic solvents and purified by chromatography. Th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.3.394
更新日期:1984-09-01 00:00:00
abstract::Using J774 macrophages, the intracellular activities of gentamicin, azithromycin, telithromycin, ciprofloxacin, moxifloxacin, and oritavancin (LY333328) against Staphylococcus aureus (strain ATCC 25923) have been quantitatively assessed in a 24-h model. S. aureus was positively localized in phagolysosomes by confocal ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.7.2283-2292.2003
更新日期:2003-07-01 00:00:00