Abstract:
:The resistance of Mycobacterium tuberculosis to isoniazid (INH) is largely linked to suppression of a catalase-peroxidase enzyme (KatG) that activates INH. In the absence of KatG, antioxidant protection is provided by enhanced expression of the peroxiredoxin AhpC, which is itself reduced by AhpD, a protein with low alkylhydroperoxidase activity of its own. Inhibition of AhpD might therefore impair the antioxidant protection afforded by AhpC and make KatG-negative strains more sensitive to oxidative stress. We report here that the 3(E),17-dioxime of testosterone is a potent competitive AhpD inhibitor, with a K(i) of 50 +/- 2 nM. The inhibitor is stereospecific, in that the 3(E) but not 3(Z) isomer is active. Computational studies provide support for a proposed AhpD substrate binding site. However, the inhibitor does not completely suppress the in vitro activity of AhpC/AhpD, because a low titer of AhpD suffices to maintain AhpC activity. This finding, and the low solubility of the inhibitor, explains its inability to suppress the growth of INH-resistant M. tuberculosis in infected mouse lungs.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Koshkin A,Zhou XT,Kraus CN,Brenner JM,Bandyopadhyay P,Kuntz ID,Barry CE 3rd,Ortiz de Montellano PRdoi
10.1128/AAC.48.7.2424-2430.2004subject
Has Abstractpub_date
2004-07-01 00:00:00pages
2424-30issue
7eissn
0066-4804issn
1098-6596pii
48/7/2424journal_volume
48pub_type
杂志文章abstract::The relative therapeutic effects of vidarabine (9-beta-D-arabinofuranosyladenine), cyclaradine (the adenosine deaminase-resistant carbocyclic analog of vidarabine), and cyclaradine-5'-methoxyacetate in the parenteral treatment of systemic herpes simplex virus type 1 infections in Swiss mice were determined. Among cont...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.4.538
更新日期:1983-10-01 00:00:00
abstract::Enterovirus 71 is one of the most important pathogens in the family of Picornaviridae that can cause severe complications in the postpoliovirus era, such as encephalitis, pulmonary edema, and even death. Pyridyl imidazolidinone is a novel class of potent and selective human enterovirus 71 inhibitor. Pyridyl imidazolid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3523-3529.2004
更新日期:2004-09-01 00:00:00
abstract::The present study was designed to determine the temporal changes in tobramycin nephrotoxicity during the dark and the light periods of the day and to look for the mechanisms of such changes. Female Sprague-Dawley rats (9 to 11 weeks old) were housed in a 14-h-light-10-h-dark cycle (lights on 0600 to 2000 h). A bolus o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.1.54
更新日期:1994-01-01 00:00:00
abstract::We have studied the interference of roxithromycin with NADPH oxidase, the key enzymatic system for oxidant production by human neutrophils. Roxithromycin alters the reconstitution of an active enzyme and impairs the translocation to the outer membrane of the cytosolic components p47-phox and p67-phox. Interestingly, i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.7.2986-2989.2005
更新日期:2005-07-01 00:00:00
abstract::To test the hypothesis that establishing gastrointestinal colonization with multiresistant Enterococcus faecium (VRE) C68 results from expansion of the enterococcal population in the upper small bowel, we compared VRE quantities recovered from the proximal, middle, and distal segments of the small bowel from mice trea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00125-06
更新日期:2006-09-01 00:00:00
abstract::RBx 11760, a bi-aryl oxazolidinone, was investigated for antibacterial activity against Gram-positive bacteria. The MIC90s of RBx 11760 and linezolid against Staphylococcus aureus were 2 and 4 mg/liter, against Staphylococcus epidermidis were 0.5 and 2 mg/liter, and against Enterococcus were 1 and 4 mg/liter, respecti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00453-16
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abstract::Difloxacin, A-56620, cefazolin, cefotaxime, ceftizoxime, cephapirin, SK&F 88070, and spectinomycin were used to compare the in vitro susceptibilities of Mycobacterium avium-M. intracellular isolates from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and diseased animals. Against the i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1390
更新日期:1990-07-01 00:00:00
abstract::Francisella tularensis, a bacterium which causes tularemia in humans, is classified as a CDC category A bioterrorism agent. In this study, we demonstrate that celecoxib, an anti-inflammatory cyclooxygenase-2 inhibitor in clinical use, exhibits activity against a type A strain of F. tularensis (Schu S4), the live vacci...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00048-09
更新日期:2009-07-01 00:00:00
abstract::Ceftolozane-tazobactam, a combination of the novel antipseudomonal cephalosporin ceftolozane and the well-established extended-spectrum β-lactamase inhibitor tazobactam, is approved for treating complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI) in adults. To determine doses ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02578-18
更新日期:2019-05-24 00:00:00
abstract::This study compared nine susceptibility testing methods and 12 endpoints for anidulafungin, caspofungin, and micafungin with the same collection of blinded FKS hot spot mutant (n = 29) and wild-type isolates (n = 94). The susceptibility tests included EUCAST Edef 7.1, agar dilution, Etest, and disk diffusion with RPMI...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01256-09
更新日期:2010-01-01 00:00:00
abstract::Filibuvir and VX-222 are nonnucleoside inhibitors (NNIs) that bind to the thumb II allosteric pocket of the hepatitis C virus (HCV) RNA-dependent RNA polymerase. Both compounds have shown significant promise in clinical trials and, therefore, it is relevant to better understand their mechanisms of inhibition. In our s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05438-11
更新日期:2012-02-01 00:00:00
abstract::Isoxyl (ISO), a thiourea derivative that was successfully used for the clinical treatment of tuberculosis during the 1960s, is an inhibitor of the synthesis of oleic and mycolic acids in Mycobacterium tuberculosis. Its effect on oleic acid synthesis has been shown to be attributable to its inhibitory activity on the s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00433-07
更新日期:2007-11-01 00:00:00
abstract::Acute kidney injury (AKI) occurs in a substantial proportion of critically ill patients receiving intravenous colistin. In the pharmacokinetic/toxicodynamic analysis reported here, the relationship of the occurrence of AKI to exposure to colistin and a number of potential patient factors was explored in 153 critically...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.01367-17
更新日期:2017-10-24 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
abstract::The antimalarial drug quinine has been shown to impair human polymorphonuclear leukocyte (PMN) functions. To gain insight into the mechanism of this phenomenon, we investigated quinine uptake by PMN with a fluorometric assay based on the fluorescence properties of this drug. After 30 min of incubation at 37 degrees C ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.7.1474
更新日期:1991-07-01 00:00:00
abstract::The experimental model of infected fibrin clots in rabbits was used to study the penetration and in vivo activity of cefixime against Klebsiella pneumoniae, Escherichia coli, and Staphylococcus aureus. The respective MICs of cefixime against these strains were 0.25, 2, and 8 micrograms/ml. The clots were infected with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.913
更新日期:1986-12-01 00:00:00
abstract::The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacok...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1128/AAC.00425-10
更新日期:2010-10-01 00:00:00
abstract::WR99210, a dihydrofolate reductase inhibitor, has promising in vitro activity against Mycobacterium avium complex (MAC). The in vitro activities of WR99210 alone and in combination with a fixed concentration of dapsone (0.5 microgram/ml) were evaluated against 35 clinical MAC isolates by a broth dilution method. The M...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1996-11-01 00:00:00
abstract::TBR-652 is a novel CCR5 antagonist with potent in vitro anti-HIV activity. The objective of this study was to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of TBR-652 in HIV-1-infected, antiretroviral treatment-experienced, CCR5 antagonist-naïve patients. A double-blind, placebo-controlled, randomized,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
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更新日期:2011-06-01 00:00:00
abstract::Structure-function relationships in antimicrobial peptides have been extensively investigated in order to obtain improved analogs. Most of these studies have targeted either alpha-helical peptides or beta-sheet peptides with multiple disulfide bridges. Tigerinins are short, nonhelical antimicrobial peptides with a sin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.7.2279-2283.2002
更新日期:2002-07-01 00:00:00
abstract::The emergence in the United States of resistance to expanded-spectrum cephalosporin (e.g., ceftriaxone) within the salmonellae has been associated primarily with three large (>100-kb) plasmids (designated types A, B, and C) and one 10.1-kb plasmid (type D) that carry the blaCMY-2 gene. In the present study, the distri...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.8.2845-2852.2004
更新日期:2004-08-01 00:00:00
abstract::Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patient...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:2014-11-01 00:00:00
abstract::The objective of this study is to evaluate the results of single-day doxycycline therapy for Mediterranean spotted fever (MSF). This is a prospective cohort study of cases with confirmed MSF treated with the single-day doxycycline regimen in a teaching hospital from 1990 to 2015. Patients received two oral doses of 20...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00978-18
更新日期:2018-10-24 00:00:00
abstract::The in vitro susceptibilities of 11 strains of Chlamydia pneumoniae to azithromycin, clarithromycin, erythromycin, L-oflaxacin, and doxycycline were determined. Clarithromycin was the most active agent tested, with an MIC for 90% of strains and minimal chlamydiacidal concentration for 90% of strains of 0.03 microns/ml...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.7.1573
更新日期:1992-07-01 00:00:00
abstract::The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified ti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.5.630
更新日期:1984-05-01 00:00:00
abstract::Inter- and intralaboratory reproducibility of susceptibility testing requires stable control strains. The Food and Drug Administration diffusion procedure recommends the Seattle strains of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) for this purpose. It was of interest to determine the present...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.3.436
更新日期:1976-09-01 00:00:00
abstract::Depending on the spacing of their positive charges, ionenes, a class of quaternary ammonium polymers, increased the interferon-inducing activity of poly(inosinic acid).poly(cytidylic acid) in mouse L-929 cells, whereas they did not enhance poly(inosinic acid).poly(cytidylic acid) induced interferon production in prima...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.4.756
更新日期:1977-04-01 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::Actithiazic acid and alpha-methyldethiobiotin inhibited the conversion of dethiobiotin to biotin resting-cell suspensions of Escherichia coli. The concentrations which effected 50% inhibition were 0.45 and 1.1 microM for actithiazic acid and alpha-methyldethiobiotin, respectively. Cells grown in low concentrations of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.1.5
更新日期:1982-01-01 00:00:00
abstract::Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefix...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05760-11
更新日期:2012-03-01 00:00:00