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 target for novel antifungals. We show that ebselen [2-phenyl-1,2-benzoselenazol-3(2H)-one] is an inhibitor of A. fumigatus TrxR (Ki = 0.22 μM) and inhibits growth of Aspergillus spp., with in vitro MIC values of 16 to 64 µg/ml. Mass spectrometry analysis demonstrates that ebselen interacts covalently with a catalytic cysteine of TrxR, Cys148. We also present the X-ray crystal structure of A. fumigatus TrxR and use in silico modeling of the enzyme-inhibitor complex to outline key molecular interactions. This provides a scaffold for future design of potent and selective antifungal drugs that target TrxR, improving the potency of ebselen toward inhbition of A. fumigatus growth.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Marshall AC,Kidd SE,Lamont-Friedrich SJ,Arentz G,Hoffmann P,Coad BR,Bruning JBdoi
10.1128/AAC.02281-18subject
Has Abstractpub_date
2019-02-26 00:00:00issue
3eissn
0066-4804issn
1098-6596pii
AAC.02281-18journal_volume
63pub_type
杂志文章abstract::The in vitro activity of moxifloxacin against 923 recent anaerobic isolates obtained from pretreatment cultures in patients with complicated intra-abdominal infections was studied using the CLSI M11-A-6 agar dilution method. Moxifloxacin was active against 87% (96 of 110) Bacteroides fragilis strains at < or = 1 micro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.4.1007
更新日期:1995-04-01 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:1994-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.2.480-489.2006
更新日期:2006-02-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.4.839
更新日期:1993-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01102-12
更新日期:2012-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01030-16
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00465-20
更新日期:2020-10-20 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:1977-11-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.11.2529
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2010-01-01 00:00:00
abstract::Helicobacter pylori is killed in vitro by polyoxyethylene acyl esters and ethers similar to simethicone emulsifiers in therapeutic antifoams. The MBC of these compounds for Helicobacter pylori was less than 20 micrograms/ml, while other gram-negative bacteria were unaffected by much higher concentrations of up to 50 m...
journal_title:Antimicrobial agents and chemotherapy
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abstract::Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts through inhibition of a P-450 enzyme undertaking sterol 14alpha demethylation. In vitro resistance in Aspergillus fumig...
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abstract::The macrolide resistance gene erm(T) was identified for the first time in a porcine Erysipelothrix rhusiopathiae isolate from swine in China. The novel 3,749-bp small plasmid pER29, which carries erm(T), had a G+C content of 31% and four distinct open reading frames. The presence of pER29 increased by at least 128-fol...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2015-04-01 00:00:00
abstract::Hepatitis C virus (HCV) NS3 protease inhibitors (PIs) are important components of novel HCV therapy regimens. Studies of PI resistance initially focused on genotype 1. Therefore, knowledge about the determinants of PI resistance for the highly prevalent genotypes 2 to 6 remains limited. Using Huh7.5 cell culture-infec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::The emergence of artemisinin-resistant Plasmodium falciparum poses a major threat to current frontline artemisinin combination therapies. Artemisinin resistance is widely associated with mutations in the P. falciparum Kelch13 (PfKelch13) propeller region, leading to delayed parasite clearance and increased survival of...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2019-03-27 00:00:00
abstract::Highly drug-resistant Salmonella enterica serovar Indiana became the most common serovar in broilers with diarrhea in China over the course of this study (15% in 2010 to 70% in 2014). While most S. Indiana isolates (87%, 384/440) were resistant to 13 to 16 of the 16 antibiotics tested, 89% of non-S. Indiana isolates (...
journal_title:Antimicrobial agents and chemotherapy
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abstract::The aim of this study was to investigate the variability of the voriconazole plasma level and its relationships with clinical outcomes and adverse events among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included, and vo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::Vulvovaginal candidiasis (VVC) is a global health problem affecting ∼75% of women at least once in their lifetime. Here we examined the epidemiology of VVC in a patient cohort to identify the causative organisms associated with VVC. Biofilm-forming capacity and antifungal sensitivity profiles were also assessed. We re...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2017-08-24 00:00:00