Abstract:
:Methionine gamma-lyase, the enzyme which catalyzes the single-step conversion of methionine to alpha-ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploited as a drug target by prodrugs that are exclusively activated by it. Trifluoromethionine was confirmed as such a prodrug and shown to be highly toxic in vitro to the anaerobic protozoan parasite Trichomonas vaginalis, to anaerobic bacteria containing methionine gamma-lyase, and to Escherichia coli expressing the trichomonad gene. The compound also has exceptional activity against the parasite growing in vivo, with a single dose preventing lesion formation in five of the six mice challenged. These findings suggest that trifluoromethionine represents a lead compound for a novel class of anti-infective drugs with potential as chemotherapeutic agents against a range of prokaryotic and eukaryotic anaerobic pathogens.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Coombs GH,Mottram JCdoi
10.1128/AAC.45.6.1743-1745.2001subject
Has Abstractpub_date
2001-06-01 00:00:00pages
1743-5issue
6eissn
0066-4804issn
1098-6596journal_volume
45pub_type
杂志文章abstract::Beta-lactam resistance in Pseudomonas aeruginosa detected only during ceftazidime therapy of cystic fibrosis patients was studied. Evaluation of resistant and susceptible isolates from one patient and resistant laboratory derivatives indicated that elevated beta-lactamase levels were the primary determinant of resista...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.9.1438
更新日期:1987-09-01 00:00:00
abstract::Aspergillus fumigatus infections are associated with high mortality rates and high treatment costs. Limited available antifungals and increasing antifungal resistance highlight an urgent need for new antifungals. Thioredoxin reductase (TrxR) is essential for maintaining redox homeostasis and presents as a promising ta...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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abstract::Teicoplanin is an investigational glycopeptide antibiotic that is structurally and microbiologically similar to vancomycin. Since teicoplanin possesses a very long elimination half-life, the manufacturer suggests that the drug be administered every 12 h for the first day of therapy and once daily thereafter. We studie...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.11.2114
更新日期:1990-11-01 00:00:00
abstract::The macrolide-aminoglycoside-streptothricin (MAS) element, an ∼4.2-kb insertion containing erm(B) and aphA3 resistance determinants, distinguishes Streptococcus pneumoniae transposon Tn1545/Tn6003 from Tn6002. Here, it is shown to be an unstable genetic element that, although it lacks recombinase genes, can exploit lo...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01487-12
更新日期:2012-11-01 00:00:00
abstract::The MICs of echinocandins against Candida isolates with fks mutations are higher than those for wild-type (WT) isolates. However, the MIC ranges for susceptible and mutant populations overlap or are poorly separated. It was recently reported that a greater separation could be achieved in the presence of serum. To more...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01364-10
更新日期:2011-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.20.4.437
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abstract::We determined the nucleotide sequence of a 6-kb DNA region harboring the recF, orf192, gyrB, and gyrA genes from Mycobacterium smegmatis mc(2)155. The amino acid sequences deduced from gyrA and gyrB displayed 89 and 86% identity, respectively, with the DNA gyrase from Mycobacterium tuberculosis, and 67 and 65% identit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.2054
更新日期:1996-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.23.3.495
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.11.6.1042
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.7.992
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abstract::The activity of azlocillin and mezlocillin, new semisynthetic ureido penicillins, was investigated and compared with that of other known beta-lactam antibiotics. At a concentration of 25 mug/ml, azlocillin inhibited 74% of Enterobacter, 97% of Proteus mirabilis, 64% of Citrobacter, 91% of Pseudomonas aeruginosa, and 8...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.13.6.930
更新日期:1978-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00461-19
更新日期:2019-08-23 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::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
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doi:10.1128/aac.46.6.1647-1650.2002
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abstract::A total of 100 and 97% of Haemophilus influenzae type b strains from major infections were susceptible, respectively, to levels of rifampin and sulfisoxazole attainable in saliva. It is theoretically feasible to eliminate Haemophilus influenzae from the nasopharynx with these drugs. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.6.969
更新日期:1978-06-01 00:00:00
abstract::We evaluated the in vitro activity of polymyxin B plus imipenem, meropenem, or tigecycline against six KPC-2-producing Enterobacteriaceae strains with high MICs for these antimicrobial agents. Polymyxin B with carbapenems, especially meropenem, were the most active combinations for Klebsiella pneumoniae and Enterobact...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00365-15
更新日期:2015-01-01 00:00:00
abstract::The gyrA and gyrB genes of Chlamydia pneumoniae TW-183 were cloned, and their proteins were purified by use of a fusion system with a maltose-binding protein. The 50% inhibitory concentrations of garenoxacin, sparfloxacin, moxifloxacin, gatifloxacin, and levofloxacin were 10.1, 47.5, 39.6, 64.2, and 156.9 microg/ml, r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.7.2327-2329.2003
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00609-07
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2005-02-01 00:00:00
abstract::PER-2 was the first detected and the second most prevalent extended-spectrum beta-lactamase in clinical pathogens isolated in Argentina and was also reported only in other South American countries. Citrobacter freundii 33587 was isolated in 1999 in Buenos Aires and was resistant to all tested beta-lactams except cepha...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01395-06
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1974-09-01 00:00:00
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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
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00972-09
更新日期:2010-01-01 00:00:00
abstract::A new method for the analysis of serum chloramphenicol by reversed-phase, high-performance liquid chromatography (HPLC) is described. The method involves a preliminary extraction of 0.1 ml of serum with ethyl acetate containing an internal standard, chromatography with a reversed-phase C18 microparticulate column with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.3.439
更新日期:1978-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1995-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01760-18
更新日期:2018-12-21 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.3.281
更新日期:1975-03-01 00:00:00
abstract::Extensive biochemical testing and 16S rRNA and rpoB sequence analysis revealed that clinical strain CF01Ent1, initially identified as Buttiauxella agrestis by the use of Api 32 biochemical strips, is a new organism in the Enterobacteriaceae family. It produced an inducible AmpC-type beta-lactamase whose sequence share...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.10.3316-3319.2002
更新日期:2002-10-01 00:00:00