Abstract:
:In order to probe the structure and function of the mycobacterial catalase-peroxidase enzyme (KatG), we employed a genetic approach using dominant-negative analysis of katG merodiploids. Transformation of Mycobacterium bovis BCG with various katG point mutants (expressed from low-copy-number plasmids) resulted in reductions in peroxidase and catalase activities as measured in cell extracts. These reductions in enzymatic activity usually correlated with increased resistance to the antituberculosis drug isoniazid (INH). However, for the N138S trans-dominant mutant, the catalase-peroxidase activity was significantly decreased while the sensitivity to INH was retained. trans-dominance required katG expression from multicopy plasmids and could not be demonstrated with katG mutants integrated elsewhere on the wild-type M. bovis BCG chromosome. Reversal of the mutant phenotype through plasmid exchange suggested the catalase-peroxidase deficiency occurred at the protein level and that INH resistance was not due to a second site mutation(s). Electrophoretic analysis of KatG proteins from the trans-dominant mutants showed a reduction in KatG dimers compared to WT and formation of heterodimers with reduced activity. The mutants responsible for these defects cluster around proposed active site residues: N138S, T275P, S315T, and D381G. In an attempt to identify mutants that might delimit the region(s) of KatG involved in subunit interactions, C-terminal truncations were constructed (with and without the D381G dominant-negative mutation). None of the C-terminal deletions were able to complement a DeltakatG strain, nor could they cause a dominant-negative effect on the WT. Taken together, these results suggest an intricate association between the amino- and carboxy-terminal regions of KatG and may be consistent with a domain-swapping mechanism for KatG dimer formation.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
DeVito JA,Morris Sdoi
10.1128/aac.47.1.188-195.2003subject
Has Abstractpub_date
2003-01-01 00:00:00pages
188-95issue
1eissn
0066-4804issn
1098-6596journal_volume
47pub_type
杂志文章abstract::In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated. MICs of 30 antimicrobial agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis H37Ra, and Mycobacter...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.1004
更新日期:1997-05-01 00:00:00
abstract::We investigated the evolution of resistance to the antifungal drug itraconazole in replicate populations of Aspergillus fumigatus that were founded from a strain with a genotype of sensitivity to a single drug and then propagated under uniform conditions. For each population, conidia were serially transferred 10 times...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.11.4405-4413.2004
更新日期:2004-11-01 00:00:00
abstract::Violacein is a violet pigment extracted from the gram-negative bacterium Chromobacterium violaceum. It presents bactericidal, tumoricidal, trypanocidal, and antileishmanial activities. We show that micromolar concentrations efficiently killed chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro;...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00693-08
更新日期:2009-05-01 00:00:00
abstract::Mitochondrial dysfunction in pathogenic fungi or model yeast causes altered susceptibilities to antifungal drugs. Here we have characterized the role of mitochondrial complex I (CI) of Candida albicans in antifungal susceptibility. Inhibitors of CI to CV, except for CII, increased the susceptibility of both patient an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01520-12
更新日期:2013-01-01 00:00:00
abstract::Ovotransferrin immobilized by covalent linkage to Sepharose 4B showed a bacteriostatic effect towards Escherichia coli similar to that of free ovotransferrin. The growth of the bacteria, after exposure to the gel-bound ovotransferrin and its removal, depended on the length of exposure. The results suggest that the ant...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.5.840
更新日期:1982-05-01 00:00:00
abstract::The aim of this study was to determine the penetration of doripenem administered intravenously into the rabbit aqueous and vitreous humors. Nineteen New Zealand White rabbits received a 20-mg dose of doripenem intravenously over 60 min. Specimens of aqueous humor, vitreous humor, and blood were obtained 30 min (n = 5)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06329-11
更新日期:2012-07-01 00:00:00
abstract::Ninety-four patients with recurrences of genital herpes were randomized in a double-blind trial to receive topical therapy for 5 days with either alpha-2a interferon at 30 X 10(6) IU/ml or 10 X 10(6) IU/ml or placebo six times daily. No differences were noted between either interferon dose and placebo with respect to ...
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.31.7.1137
更新日期:1987-07-01 00:00:00
abstract::Many Pseudomonas aeruginosa isolates from the airways of patients with cystic fibrosis (CF) are sensitive to antibiotics in susceptibility testing, but eradication of the infection is difficult. The main reason is the biofilm formation in the airways of patients with CF. The pharmacokinetics (PKs) and pharmacodynamics...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06486-11
更新日期:2012-05-01 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::A new natural TEM-2 derivative, named TEM-72, was identified in a Proteus mirabilis strain and in a Morganella morganii strain isolated in Italy in 1999. Compared to TEM-1, TEM-72 contains the following amino acid substitutions: Q39K, M182T, G238S, and E240K. Kinetic analysis showed that TEM-72 exhibits an extended-sp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.9.2537-2539.2000
更新日期:2000-09-01 00:00:00
abstract::We characterized the stability of a plasmid pCP53-mcr1_3 encoding mcr-1 and mcr-3.19 with and without colistin exposure during cultural passages via S1-pulsed-field gel electrophoresis (PFGE) and nanopore MinION sequencing. Both mcr-1 and mcr-3.19 were missing in certain subclones, mediated by genetic excision (ISApl1...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01002-19
更新日期:2019-08-23 00:00:00
abstract::Activity against the coccidial pathogen Eimeria tenella in chickens has been discovered among alpha 2 adrenergic agonists. The clonidine analog 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine was active in feed at 7.5 ppm, a concentration similar to the use levels of potent commercial agents, e.g., maduramicin. A...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.2.368
更新日期:1992-02-01 00:00:00
abstract::The current voriconazole dosing recommendation in adolescents is based on limited efficacy and pharmacokinetic data. To confirm the appropriateness of dosing adolescents like adults, a pharmacokinetic study was conducted in 26 immunocompromised adolescents aged 12 to <17 years following intravenous (IV) voriconazole t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.05010-11
更新日期:2011-12-01 00:00:00
abstract::Assessment of drug susceptibility has become an integral part of influenza virus surveillance. In this study, we describe the drug resistance profile of influenza A(H3N2) virus, A/Mississippi/05/2011, collected from a patient treated with oseltamivir and detected via surveillance. An MDCK cell-grown isolate of this vi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01364-13
更新日期:2013-12-01 00:00:00
abstract::Acanthamoeba spp. are the causative agents of Acanthamoeba keratitis (AK), which mainly occurs in contact lens wearers, and of skin lesions, granulomatous amoebic encephalitis (GAE), and disseminating diseases in the immunocompromised host. AK therapy is complex and irritating for the eye, skin lesions are difficult t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00715-07
更新日期:2008-02-01 00:00:00
abstract::Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01529-07
更新日期:2008-04-01 00:00:00
abstract::Effervescent lozenges containing 10 mg of zinc acetate were evaluated as a treatment of upper respiratory tract infections in a double-blind randomized trial by using a placebo which was indistinguishable to most observers in taste and appearance from the active material. Of the 70 treatment courses used by 55 individ...
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.31.8.1263
更新日期:1987-08-01 00:00:00
abstract::Recently, a novel variant of mecA known as mecC (mecA(LGA251)) was identified in Staphylococcus aureus isolates from both humans and animals. In this study, we identified a Staphylococcus xylosus isolate that harbors a new allotype of the mecC gene, mecC1. Whole-genome sequencing revealed that mecC1 forms part of a cl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01882-12
更新日期:2013-03-01 00:00:00
abstract::The in vitro activities of CG400549, a novel FabI inhibitor, were compared to those of linezolid and commonly used antimicrobials against recent bacterial isolates. CG400549 had an MIC(90) of 0.5 microg/ml for Staphylococcus aureus strains and was more potent than either linezolid or vancomycin. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01562-06
更新日期:2007-07-01 00:00:00
abstract::The in vitro activity of GR-20263, a new aminothiazolyl cephalosporin, was compared with the activities of other beta-lactam antibiotics by using 800 clinical bacterial isolates. GR-20263 was highly active (inhibition of 90% of the isolates between 0.03 and 1 microgram/ml) against the common Enterobacteriaceae and 5 t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.5.807
更新日期:1980-05-01 00:00:00
abstract::We describe outcomes of patients with infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01569-15
更新日期:2015-11-09 00:00:00
abstract::Among 477 patients with susceptible Enterobacter spp., 49 subsequently harbored third-generation cephalosporin-resistant Enterobacter spp. Broad-spectrum cephalosporins were independent risk factors for resistance (relative risk [OR] = 2.3, P = 0.01); quinolone therapy was protective (OR = 0.4, P = 0.03). There were t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.45.9.2628-2630.2001
更新日期:2001-09-01 00:00:00
abstract::The mechanism of colistin resistance (Col(r)) in Acinetobacter baumannii was studied by selecting in vitro Col(r) derivatives of the multidrug-resistant A. baumannii isolate AB0057 and the drug-susceptible strain ATCC 17978, using escalating concentrations of colistin in liquid culture. DNA sequencing identified mutat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00284-09
更新日期:2009-09-01 00:00:00
abstract::The most appropriate vancomycin dosing strategy in pediatric patients weighing ≥70 kg (weight based versus non-weight based) to achieve an area under the concentration-time curve (AUC) of ≥400 mg·liter/h and a trough concentration of <20 mg/liter is not known. Population pharmacokinetic analysis determined that dosing...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02359-18
更新日期:2019-03-27 00:00:00
abstract::Viomycin-resistant strains isolated from Mycobacterium smegmatis demonstrated pleiotropic resistance to tuberactinomycin-N, capreomycin, streptomycin, and kanamycin as a result of mutational alteration of ribosomes, even though they were selected for resistance to a single antibiotic. The pleiotropic drug resistance o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.1.46
更新日期:1974-07-01 00:00:00
abstract::Anidulafungin is an echinocandin with activity against Candida species and Aspergillus species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children. A m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.50.2.632-638.2006
更新日期:2006-02-01 00:00:00
abstract::The in vitro activities of a new quinolone, WIN 57273, and the combination of piperacillin and tazobactam, a beta-lactamase inhibitor, were compared with those of cefoxitin, ceftizoxime, chloramphenicol, clindamycin, imipenem, metronidazole, and piperacillin for 123 clinical anaerobic isolates. Ceftizoxime and cefoxit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.9.1858
更新日期:1990-09-01 00:00:00
abstract::Plasmid-mediated mechanisms, comprising TEM hyperproduction, TEM derivative production, and OXA production, lead to amoxicillin-clavulanic acid resistance in enterobacteria. The ability of the single-strand conformation polymorphism (SSCP)-PCR method to differentiate the genes encoding inhibitor-resistant beta-lactama...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.4.879
更新日期:1998-04-01 00:00:00
abstract::The EmbCAB proteins have been considered a target for ethambutol (EMB). Mutations in embCAB are known to confer most EMB resistance. However, the knowledge about the effects of embCAB mutations on the EMB resistance level and about the role of mutation-mutation interactions is limited in China. Here, we sequenced embC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01279-17
更新日期:2017-12-21 00:00:00
abstract::Staphylococcus aureus bacteremia (SAB) causes high rates of morbidity and death. Several studies in academic health settings have demonstrated that consultations from infectious diseases specialists improve the quality of care and clinical outcomes for SAB. Few data that describe the impact in resource-limited setting...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00439-16
更新日期:2016-09-23 00:00:00