Abstract:
:The apicomplexan parasites Cryptosporidium and Toxoplasma are serious threats to human health. Cryptosporidiosis is a severe diarrheal disease in malnourished children and immunocompromised individuals, with the only FDA-approved drug treatment currently being nitazoxanide. The existing therapies for toxoplasmosis, an important pathology in immunocompromised individuals and pregnant women, also have serious limitations. With the aim of developing alternative therapeutic options to address these health problems, we tested a number of benzoxaboroles, boron-containing compounds shown to be active against various infectious agents, for inhibition of the growth of Cryptosporidium parasites in mammalian cells. A 3-aminomethyl benzoxaborole, AN6426, with activity in the micromolar range and with activity comparable to that of nitazoxanide, was identified and further characterized using biophysical measurements of affinity and crystal structures of complexes with the editing domain of Cryptosporidium leucyl-tRNA synthetase (LeuRS). The same compound was shown to be active against Toxoplasma parasites, with the activity being enhanced in the presence of norvaline, an amino acid that can be mischarged by LeuRS. Our observations are consistent with AN6426 inhibiting protein synthesis in both Cryptosporidium and Toxoplasma by forming a covalent adduct with tRNA(Leu) in the LeuRS editing active site and suggest that further exploitation of the benzoxaborole scaffold is a valid strategy to develop novel, much needed antiparasitic agents.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Palencia A,Liu RJ,Lukarska M,Gut J,Bougdour A,Touquet B,Wang ED,Li X,Alley MR,Freund YR,Rosenthal PJ,Hakimi MA,Cusack Sdoi
10.1128/AAC.00873-16subject
Has Abstractpub_date
2016-09-23 00:00:00pages
5817-27issue
10eissn
0066-4804issn
1098-6596pii
AAC.00873-16journal_volume
60pub_type
杂志文章abstract::We studied the influence of the lipid/amphotericin B (AMB) ratio and the phospholipid type on the in vitro renal cell toxicity and antifungal efficacy of lipid-associated AMB (L-AMB). L-AMB was prepared at one of two different lipid/AMB ratios (1 and 40) by incubating AMB with empty small unilamellar vesicles, made fr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.2.262
更新日期:1992-02-01 00:00:00
abstract::The presence and characterization of plasmid-mediated fosfomycin resistance determinants among Escherichia coli isolates collected from pets in China between 2006 and 2010 were investigated. Twenty-nine isolates (9.0%) were positive for fosA3, and all of them were CTX-M producers. The fosA3 genes were flanked by IS26 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05104-11
更新日期:2012-04-01 00:00:00
abstract::Beta-l-2',3'-didehydro-2',3'-dideoxy-N(4)-hydroxycytidine (l-Hyd4C) was demonstrated to be an effective and highly selective inhibitor of hepatitis B virus (HBV) replication in HepG2.2.15 cells (50% effective dose [ED(50)] = 0.03 microM; 50% cytotoxic dose [CD(50)] = 2,500 microM). In the present study, we investigate...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01176-09
更新日期:2010-01-01 00:00:00
abstract::Staphylococcal biofilms on surgical implants are the underlying cause of a lack of response to antimicrobial treatment. We investigated the effects of vancomycin (VAN), daptomycin (DAP), fosfomycin (FOS), tigecycline (TGC), and ceftriaxone (CRX), alone and in combination with azithromycin (AZI), on established biofilm...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01628-08
更新日期:2009-08-01 00:00:00
abstract::The effect of moxalactam and cefuroxime on mitogen-stimulated human peripheral blood mononuclear leukocytes was studied. Mononuclear leukocytes, mitogen, and antibiotic were added to microtiter wells. Cells were cultured for 3 days, pulsed with tritiated thymidine, and then counted. Compared with control cell cultures...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.3.360
更新日期:1983-03-01 00:00:00
abstract::Expression of high-level beta-lactam resistance is known to be thermosensitive in many methicillin-resistant Staphylococcus aureus (MRSA) strains, including strain COL, in which the high methicillin MIC for cultures grown at 37 degrees C (800 microg/ml) was reduced to 12 microg/ml at 42 degrees C. COL grew faster at 4...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00504-07
更新日期:2008-02-01 00:00:00
abstract::Berberine sulfate is an alkaloid extracted from the roots and bark of various plants and possesses antibacterial, antifungal, and antiprotozoal activities. Most studies have focused on the bacteriostatic or bactericidal activities of this compound. In this study, we report that berberine sulfate is bacteriostatic for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.9.1370
更新日期:1988-09-01 00:00:00
abstract::Two new antifungal triazoles, BAY n7133 and ICI 153,066, were compared with ketoconazole in treatment of mice challenged intraperitoneally with Cryptococcus neoformans. At high challenge doses, thymus-containing normal mice had prolonged survival after treatment with BAY n7133. Athymic mice, which have severely defici...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.6.829
更新日期:1983-12-01 00:00:00
abstract::Increasing mobile colistin resistance, mediated by the mcr gene family, in Enterobacteriaceae has become a global concern. Among the 10 reported mcr genes, mcr-8 was first identified in Klebsiella pneumoniae, which could cause severe infections with high mortality. Information about the prevalence and genetic context ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01872-20
更新日期:2020-12-16 00:00:00
abstract::Here, we report the first detection of carbapenemase-producing Escherichia coli in Alaska and in wildlife in the United States. Wild bird (gull) feces sampled at three locations in Southcentral Alaska yielded isolates that harbored plasmid-encoded blaKPC-2 or chromosomally encoded blaOXA-48 and genes associated with a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00758-19
更新日期:2019-07-25 00:00:00
abstract::There remains an unmet need to address the substantial morbidity and mortality associated with severe community-acquired pneumonia (sCAP). Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse animal models of infectious and noninfectious inflammation. This blinded dose-escalation safety st...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00579-20
更新日期:2020-09-21 00:00:00
abstract::An outbreak due to extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) was detected from May 1993 to June 1995. A total of 145 patients, particularly patients in intensive care units (ICUs) (107 patients [72%]), were colonized or infected. Infection developed in 92 (63%) patients, and primary ba...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.1.53
更新日期:1998-01-01 00:00:00
abstract::The generation rate constants for the steady-state growth of antibiotic-inhibited Escherichia coli have the same formal dependency on concentration for deoxylincomycin, lincomycin (phase I), erythromycin, clindamycin, and U24729A. They may be kinetically classified as a group A, in which the first three compounds comp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.4.5.574
更新日期:1973-11-01 00:00:00
abstract::Doxycycline is the treatment of choice for canine monocytic ehrlichiosis (CME), a well-characterized disease and valuable model for tick-borne zoonoses. Conflicting reports of clearance of Ehrlichia canis after treatment with doxycycline suggested that the disease phase during which treatment is initiated influences o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01622-09
更新日期:2010-12-01 00:00:00
abstract::Infection with human cytomegalovirus (HCMV) continues to be a major threat for pregnant women and the immunocompromised population. Although several anti-HCMV therapies are available, the development of new anti-HCMV agents is highly desired. There is growing interest in identifying compounds that might inhibit HCMV b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00898-12
更新日期:2012-09-01 00:00:00
abstract::The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01596-13
更新日期:2013-12-01 00:00:00
abstract::Analysis of the evolution of drug target genes under changing drug policy is needed to assist monitoring of Plasmodium falciparum drug resistance in the field. Here we genotype Pfcrt and Pfdmr1 of 700 isolates collected in French Guiana from 2000 (5 years after withdrawal of chloroquine) to 2008, i.e., the period when...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05280-11
更新日期:2012-03-01 00:00:00
abstract::A patient with AIDS and chronic diarrhea caused by Enterocytozoon bieneusi was successfully treated with nitazoxanide, producing a complete clinical and parasitological response, while off of antiviral therapy. This suggests that nitazoxanide may be effective in treating microsporidiosis caused by E. bieneusi, a disea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.1.167-168.2000
更新日期:2000-01-01 00:00:00
abstract::The purpose of this study was to compare the activity of HMR 1043 with those of daptomycin and teicoplanin against gram-positive isolates. Susceptibility tests were performed for 52 strains, 26 parental strains, including staphylococcal, streptococcal, enterococcal, and listerial strains, and 26 HMR 1043-resistant mut...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.9.3025-3029.2003
更新日期:2003-09-01 00:00:00
abstract::Chlorhexidine (Hibiscrub; ICI) is generally accepted to be effective as an antiseptic hand wash for methicillin-susceptible Staphylococcus aureus (MSSA), but there is dispute whether the chlorhexidine MIC for methicillin-resistant S. aureus (MRSA) strains is higher than that for MSSA strains and, indeed, whether it is...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.10.1997
更新日期:1991-10-01 00:00:00
abstract::The comparative in vitro activity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-defined Clostridium difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C. difficile iso...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01136-13
更新日期:2013-10-01 00:00:00
abstract::The impact of acidification and alkalinization of the urine on the pharmacokinetics of cinoxacin was examined after single 500-mg oral doses were administered to nine healthy male volunteers. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride or sodium bicarbonate, respectively. P...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.472
更新日期:1982-03-01 00:00:00
abstract::Rabbits with Staphylococcus aureus endocarditis were treated with cephalothin or ceftazidime to determine whether differences in in vitro activity would result in differences in in vivo efficacy. Antibiotics were administered in doses equivalent to maximum recommended human doses, and results of laboratory tests to pr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.2.231
更新日期:1984-08-01 00:00:00
abstract::The in vitro activity of TR-700 (torezolid) was evaluated against a collection of 660 staphylococcal blood isolates. TR-700 showed excellent activity against all the staphylococci tested. The MIC(50) and MIC(90) values of TR-700, linezolid, daptomycin, and vancomycin against methicillin-resistant Staphylococcus aureus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01653-09
更新日期:2010-05-01 00:00:00
abstract::Chloramphenicol acetyltransferases specified by fi(-) (F fertility-noninhibiting) R factors were compared with those specified by the fi(+) R factors R1, 222, and R6-S. Three classes of enzyme were distinguished: class I was determined by group N fi(-) R factors and was indistinguishable from the enzyme determined by ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.1.99
更新日期:1973-01-01 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::The in vitro activities of eight antifungal drugs against clinical isolates of Fonsecaea pedrosoi (n = 21), Fonsecaea monophora (n = 25), and Fonsecaea nubica (n = 9) were tested. The resulting MIC(90)s for all strains (n = 55) were as follows, in increasing order: posaconazole, 0.063 microg/ml; itraconazole, 0.125 mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01655-09
更新日期:2010-04-01 00:00:00
abstract::The new fluoroquinolone trovafloxacin was tested against a ciprofloxacin-sensitive, methicillin-resistant Staphylococcus aureus strain in the rabbit model of endocarditis. Trovafloxacin was more effective than vancomycin (CFU/g of vegetation, 2.65 +/- 1.87 versus 4.54 +/- 2.80 [mean +/- standard deviation]; P < 0.05) ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3325
更新日期:1998-12-01 00:00:00
abstract::Stereoselective disposition of sulbenicillin (SBPC) epimers in healthy human volunteers was studied in order to clarify the differences in pharmacokinetic behavior between the epimers. Stereospecific high-performance liquid chromatography was used for the determination of SBPC epimers. Plasma protein binding was measu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Clostridium difficile is the most frequently identified enteric pathogen in patients with nosocomially acquired, antibiotic-associated diarrhea. The drugs most commonly used to treat diseases associated with C. difficile are metronidazole and vancomycin. Most clinical laboratories assume that all C. difficile isolates...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.6.1647-1650.2002
更新日期:2002-06-01 00:00:00