Abstract:
:Alveolar echinococcosis (AE) is a severe disease caused by the larval stage of the tapeworm Echinococcus multilocularis Current chemotherapeutic treatment options based on benzimidazoles are of limited effectiveness, which underlines the need to find new antiechinococcosis drugs. Metformin is an antihyperglycemic and antiproliferative agent that shows activity against the related parasite Echinococcus granulosus Hence, we assessed the in vitro and in vivo effects of the drug on E. multilocularis Metformin exerted significant dose-dependent killing effects on in vitro cultured parasite stem cells and protoscoleces and significantly reduced the dedifferentiation of protoscoleces into metacestodes. Likewise, oral administration of metformin (50 mg/kg of body weight/day for 8 weeks) was effective in achieving a significant reduction of parasite weight in a secondary murine AE model. Our results revealed mitochondrial membrane depolarization, activation of Em-AMPK, suppression of Em-TOR, and overexpression of Em-Atg8 in the germinal layer of metformin-treated metacestode vesicles. The opposite effects on the level of active Em-TOR in response to exogenous insulin and rapamycin suggest that Em-TOR is part of the parasite's insulin signaling pathway. Finally, the presence of the key lysosomal pathway components, through which metformin reportedly acts, was confirmed in the parasite by in silico assays. Taken together, these results introduce metformin as a promising candidate for AE treatment. Although our study highlights the importance of those direct mechanisms by which metformin reduces parasite viability, it does not necessarily preclude any additional systemic effects of the drug that might reduce parasite growth in vivo.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Loos JA,Dávila VA,Brehm K,Cumino ACdoi
10.1128/AAC.01808-19subject
Has Abstractpub_date
2020-08-20 00:00:00issue
9eissn
0066-4804issn
1098-6596pii
AAC.01808-19journal_volume
64pub_type
杂志文章abstract::The Infectious Diseases Society of America advocates trimethoprim-sulfamethoxazole (SXT) as initial therapy for females with acute uncomplicated bacterial cystitis in settings where the prevalence of SXT resistance does not exceed 10 to 20%. To determine trends in the activities of SXT, ampicillin, ciprofloxacin, and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.8.2540-2545.2002
更新日期:2002-08-01 00:00:00
abstract::PCR was used to amplify a 238-bp region from Helicobacter pylori which corresponded to the quinolone resistance-determining region in Escherichia coli. The gyrA gene of H. pylori was cloned and sequenced. An open reading frame of 2,478 nucleotides coded for a polypeptide of 826 amino acids with a calculated molecular ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.107
更新日期:1995-01-01 00:00:00
abstract::Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.1.63
更新日期:1974-01-01 00:00:00
abstract::The antibiotic cerulenin markedly inhibits the growth of Escherichia coli. The effects of the antibiotic on cellular syntheses were studied by measuring the incorporation of labeled precursors into lipids and macromolecules. During the first 40 min after the addition of cerulenin to a culture of growing cells, lipid s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.5.549
更新日期:1973-05-01 00:00:00
abstract::Ten patients with acquired immunodeficiency syndrome with newly diagnosed cytomegalovirus (CMV) retinitis were treated with an induction regimen of intravenous foscarnet, 60 mg/kg of body weight, administered as a 2-h infusion and repeated every 8 h for 14 days. At the end of induction, 9 of 10 patients had stabilized...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.5.736
更新日期:1989-05-01 00:00:00
abstract::The Cpx stress response is widespread among Enterobacteriaceae We previously reported a mutation in cpxA in a multidrug-resistant strain of Klebsiella aerogenes isolated from a patient treated with imipenem. This mutation yields a single-amino-acid substitution (Y144N) located in the periplasmic sensor domain of CpxA....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00291-20
更新日期:2020-05-21 00:00:00
abstract::Patients (n = 409) with severe skin and soft tissue infections (SSTIs) were randomized to receive clinafloxacin or piperacillin-tazobactam (plus optional vancomycin for methicillin-resistant cocci), administered intravenously, with the option to switch to oral medication. Most patients had cellulitis, wound infections...
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.45.2.525-531.2001
更新日期:2001-02-01 00:00:00
abstract::Ten beta-lactamase-producing Enterococcus faecalis isolates were examined for the presence of the staphylococcal beta-lactamase repressor and antirepressor genes. Four isolates, previously shown to be unrelated to each other by pulsed-field gel electrophoresis analysis, were positive for both genes by PCR, although be...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1170
更新日期:1996-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.10.3195-3201.2003
更新日期:2003-10-01 00:00:00
abstract::The influence of vancomycin and flavophospholipol (FPL) on the transfer rate of conjugative plasmids harboring the vancomycin resistance operon vanA was determined in several clinical and animal isolates of Enterococcus faecium. FPL significantly inhibited the frequency of transfer of conjugative VanA plasmids up to 7...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.11.3189-3192.2000
更新日期:2000-11-01 00:00:00
abstract::By cloning studies and complementation experiments, the sulfonamide resistance gene of a serogroup B and serotype 15 (B:15) strain of Neisseria meningitidis was localized to a 1.2-kb chromosomal SspI fragment expressing a drug-resistant dihydropteroate synthase. The fragment hybridized to DNA from both resistant and s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.11.2277
更新日期:1990-11-01 00:00:00
abstract::Sordarin and its derivatives are antifungal compounds of potential clinical interest. Despite the highly conserved nature of the fungal and mammalian protein synthesis machineries, sordarin is a selective inhibitor of protein synthesis in fungal organisms. In cells sensitive to sordarin, its mode of action is through ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01603-07
更新日期:2008-05-01 00:00:00
abstract::Two TolC homologs, PM0527 and PM1980, were identified for Pasteurella multocida. A pm0527 mutant displayed increased susceptibility to a range of chemicals, including rifampin (512-fold) and acridine orange (128-fold). A pm1980 mutant showed increased susceptibility to rifampin, ceftazidime, and vancomycin. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00245-08
更新日期:2008-11-01 00:00:00
abstract::The inhibition of the lymphadenopathy-associated virus strain of human immunodeficiency virus (HIV) by alternating regimens of two dideoxynucleosides, 3'-azido-3'-deoxythymidine (AZT) (zidovudine) and 2',3'-dideoxycytidine (ddC), was determined in CEM cells. Cultures infected with virus for 2 h were treated with clini...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.6.920
更新日期:1989-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.49.4.1600-1603.2005
更新日期:2005-04-01 00:00:00
abstract::Acute pulmonary exacerbations (APE) involving Pseudomonas aeruginosa are associated with increased morbidity and mortality in cystic fibrosis (CF) patients. Drug resistance is a significant challenge to treatment. Ceftazidime-avibactam (CZA) demonstrates excellent in vitro activity against isolates recovered from CF p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00988-17
更新日期:2017-09-22 00:00:00
abstract::Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibito...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1326
更新日期:1990-07-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.12.2142
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2018-08-27 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
pub_type: 杂志文章
doi:10.1128/aac.37.9.1877
更新日期:1993-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01738-10
更新日期:2011-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.3.639
更新日期:1999-03-01 00:00:00
abstract::Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03543-14
更新日期:2015-02-01 00:00:00
abstract::The effects of trifluorothymidine (5-trifluoromethyl-2'-deoxyuridine, F3dThd) on the replication of three mouse cell lines, LM929, Ltk- (and LM929 derivative devoid of cytosolic deoxythymidine [dThd] kinase activity), and Ltk- c139 (a Ltk- derivative which expresses herpes simplex virus type 1-specified dThd kinase su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.5.881
更新日期:1981-05-01 00:00:00
abstract::Triazoles are first-line agents for treating aspergillosis. The prevalence of azole resistance in Aspergillus fumigatus is increasing, and cross-resistance is a growing concern. In this study, the susceptibilities of 40 A. fumigatus clinical isolates were tested by using the CLSI method with amphotericin B, itraconazo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2013-11-01 00:00:00
abstract::BEL-1 is an acquired class A extended-spectrum β-lactamase (ESBL) found in Pseudomonas aeruginosa clinical isolates from Belgium which is divergent from other ESBLs (maximum identity of 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem, and moxalactam. Crystals of BEL-1 were obt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00936-16
更新日期:2016-11-21 00:00:00
abstract::We characterized the genetic environment of mcr-1 in colistin-resistant Escherichia coli strains isolated in Switzerland during 2014 to 2016 from humans (n = 3) and chicken meat (n = 6). Whole-genome and plasmid sequencing identified the mcr-1 gene integrated in IncX4 (of which, one strain carried the mcr-1.2 variant)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01245-17
更新日期:2017-10-24 00:00:00
abstract::GSK1322322 is a novel inhibitor of peptide deformylase (PDF) with good in vitro activity against bacteria associated with community-acquired pneumonia and skin infections. We have characterized the in vivo pharmacodynamics (PD) of GSK1322322 in immunocompetent animal models of infection with Streptococcus pneumoniae a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01842-15
更新日期:2015-10-19 00:00:00
abstract::We report 2 cases of recurrent Campylobacter coli enteritis caused by macrolide- and fluoroquinolone-resistant strains in 2 patients with hypogammaglobulinemia, successfully treated with a prolonged course of fosfomycin-tromethamine with no side effects. Fosfomycin-tromethamine may be a feasible alternative therapy fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00447-16
更新日期:2016-06-20 00:00:00