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 early-ring-stage parasites. There is therefore a need to discover novel drugs that are effective against artemisinin-resistant P. falciparum In view of this, our study aimed to identify compounds from the Library of Pharmacologically Active Compounds1280 (LOPAC1280) that could increase the efficacy of artesunate and be used as a potential partner drug for treatment against artemisinin-resistant falciparum malaria. By using a modified ring-stage survival assay, we performed a high-throughput screening of the activities of the 1,280 compounds from the LOPAC library in combination with artesunate against the P. falciparum IPC 5202 field isolate harboring the R539T mutation in the PfKelch13 propeller region. The potencies of the hits against both the IPC 5202 and CamWT_C580Y field isolates were determined through dose-dependent isobologram analyses; CamWT_C580Y has the more prevalent C580Y mutation characteristic of strains with artemisinin resistance. We identified tyrphostin A9 to have synergistic and additive activity against both parasite strains when dosed in combination with artesunate. These findings provide promising novel artesunate combinations that can target the P. falciparum artemisinin-resistant ring stage and insights that may aid in obtaining a better understanding of the mechanism involved in artemisinin resistance.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Tong JX,Ang SEL,Tan EHN,Tan KSWdoi
10.1128/AAC.02389-18subject
Has Abstractpub_date
2019-03-27 00:00:00issue
4eissn
0066-4804issn
1098-6596pii
AAC.02389-18journal_volume
63pub_type
杂志文章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::Drug repurposing affords the implementation of new treatments at a moderate cost and under a faster time-scale. Most of the clinical drugs against Leishmania share this origin. The antidepressant sertraline has been successfully assayed in a murine model of visceral leishmaniasis. Nevertheless, sertraline targets in L...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01928-18
更新日期:2018-11-26 00:00:00
abstract::Enterobacteriaceae producing the Ambler class D OXA-48 carbapenemase, combined with additional resistance mechanisms, such as permeability defects or cocarriage of class A, B, or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 Enterobacteriaceae ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00592-18
更新日期:2018-11-26 00:00:00
abstract::Here we completely sequenced four mcr-1-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00550-16
更新日期:2016-06-20 00:00:00
abstract::Lactation studies are necessary evaluations of medications for reproductive-age women. We evaluated pharmacokinetics (PK), pharmacodynamics, safety, and adherence profiles associated with 7 days of 1% tenofovir (TFV) vaginal gel use during lactation. Tenofovir levels (maternal/infant serum, milk) and anti-HIV activity...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00645-16
更新日期:2016-08-22 00:00:00
abstract::Leishmania mexicana is a protozoan parasite that causes a disease in humans with frequent relapses after treatment. It is also highly resistant to the currently available drugs. For this reason, there is an urgent need for more effective antileishmanial drugs. Hydroxyurea, an anticancer drug, is toxic to replicating e...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00124-08
更新日期:2008-10-01 00:00:00
abstract::GS-9160 is a novel and potent inhibitor of human immunodeficiency virus type 1 (HIV-1) integrase (IN) that specifically targets the process of strand transfer. It is an authentic inhibitor of HIV-1 integration, since treatment of infected cells results in an elevation of two-long terminal repeat circles and a decrease...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00984-08
更新日期:2009-03-01 00:00:00
abstract::Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry in...
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.00523-15
更新日期:2015-08-01 00:00:00
abstract::We report the detection of PER-1 extended-spectrum β-lactamase (ESBL) in a clinical non-O1, non-O139 Vibrio cholerae strain from China. ISCR1-mediated bla(PER-1) was embedded in a complex In4 family class 1 integron belonging to the lineage of Tn1696 on a conjugative IncA/C plasmid. A free 8.98-kb circular molecule pr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00166-15
更新日期:2015-07-01 00:00:00
abstract::In both scid and BALB/c mouse-Leishmania donovani models, hexadecyphosphocholine (miltefosine) and AmBisome had similar levels of activity. In contrast, sodium stibogluconate (Pentostam) was significantly less active against L. donovani in scid mice than in BALB/c mice. The in vitro anti-leishmanial activity of miltef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.6.1872-1875.2001
更新日期:2001-06-01 00:00:00
abstract::We describe outcomes of patients with infections with carbapenem-resistant Klebsiella pneumoniae (CRKP) who received ertapenem-containing double-carbapenem therapy (ECDCT). Clinical success was observed in 7/18 (39%) patients overall: bloodstream infections, 3/7 (43%); pneumonia, 1/5 (20%); intraabdominal infections, ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01569-15
更新日期:2015-11-09 00:00:00
abstract::NK-2, a membrane-acting antimicrobial peptide, was derived from the cationic core region of porcine NK-lysin and consists of 27 amino acid residues. It adopts an amphipathic, alpha-helical secondary structure and has been shown to interact specifically with membranes of negatively charged lipids. We therefore investig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.5.1593-1599.2004
更新日期:2004-05-01 00:00:00
abstract::The use of gentamicin to control contamination in a tissue culture system for the isolation of Chlamydia was investigated. Gentamicin, at concentrations up to 100 mug/ml, did not appear to inhibit the growth of stock chlamydial strains, as judged by assays for iodine-staining inclusions. When 343 cervical and urethral...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.6.698
更新日期:1973-06-01 00:00:00
abstract::The accumulation of quinolones by Escherichia coli JF568, Pseudomonas aeruginosa PAO1, and Staphylococcus aureus ATCC 29213 was measured by a modified fluorometric assay (J. S. Chapman and N. H. Georgopapadakou, Antimicrob. Agents Chemother. 33:27-29, 1989). The quinolones examined were fleroxacin, pefloxacin, norflox...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.8.1601
更新日期:1992-08-01 00:00:00
abstract::The 747-bp cfiA gene, which encodes a metallo-beta-lactamase, and the regions flanking cfiA in six imipenem-resistant and four imipenem-susceptible Bacteroides fragilis strains isolated in Japan were analyzed by PCR and DNA sequencing. The nucleotide sequences of the cfiA genes (designated cfiA(1) to cfiA(10)) of all ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.3.979-985.2003
更新日期:2003-03-01 00:00:00
abstract::A beta-lactam-sensitive strain (C152) of Shigella dysenteriae showed two major outer membrane proteins (OMPs) with M(r)s of 43,000 and 38,000, while the clinical isolate M2 lacked the 43,000-Mr OMP, which acted as a channel for beta-lactam antibiotics. Permeability of beta-lactams across the outer membrane (OM) of M2 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.10.2302
更新日期:1997-10-01 00:00:00
abstract::NorC, a new efflux pump, like NorB, contributes to quinolone resistance that includes resistance to moxifloxacin and sparfloxacin in Staphylococcus aureus. norC expression, like that of norB and tet38, is negatively regulated by MgrA, and overexpression of both norC and norB contributes to the quinolone resistance phe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.3.1104-1107.2006
更新日期:2006-03-01 00:00:00
abstract::Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.04729-14
更新日期:2015-05-01 00:00:00
abstract::To determine if saquinavir mesylate (saquinavir) is a substrate of human multidrug resistance-associated protein 1 (hMRP1 [ABCC1]) or hMRP2 (cMOAT, or ABCC2), MDCKII cells that overexpress either hMRP1 (MDCKII-MRP1) or hMRP2 (MDCKII-MRP2) were used to investigate saquinavir's cytotoxicity and transport in comparison w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3456-3462.2002
更新日期:2002-11-01 00:00:00
abstract::We evaluated the efficacy, safety, and tolerance of cefotaxime in 35 adults (25 with pleuropulmonary infections, 7 with genitourinary tract infections, and 3 with soft tissue infections). Of these 35 patients, 18 (51.4%) were seriously or critically ill. In vitro susceptibility testing revealed that 90.4% of the patho...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.421
更新日期:1982-03-01 00:00:00
abstract::A combination of 3 g of ticarcillin and 200 mg of clavulanic acid was administered intravenously to six healthy male volunteers, after which the concentrations of these agents in serum and blister fluid were measured. The ratio of the two drugs in serum varied from 15:1 (ticarcillin-clavulanic acid) at the time of adm...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.6.831
更新日期:1983-06-01 00:00:00
abstract::Pseudomonas aeruginosa is equipped with the Sec and Tat protein secretion systems, which translocate the xenobiotic transporter MexAB-OprM and the pathogenic factor phospholipase C (PlcH), respectively. When the signal sequence of MexA was replaced with that of PlcH, the hybrid protein was successfully expressed and r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01495-09
更新日期:2010-04-01 00:00:00
abstract::One way to speed up the TB drug discovery process is to search for antitubercular activity among compound series that already possess some of the key properties needed in anti-infective drug discovery, such as whole-cell activity and oral absorption. Here, we present MGIs, a new series of Mycobacterium tuberculosis gy...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03913-14
更新日期:2015-04-01 00:00:00
abstract::The in vitro activity of tosufloxacin (A-61827; T-3262) against 15 clinical isolates of Chlamydia trachomatis and 31 recent clinical isolates of Neisseria gonorrhoeae, including 15 spectinomycin-resistant N. gonorrhoeae and 16 penicillinase-producing N. gonorrhoeae, was determined. Tosufloxacin was compared with doxyc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.971
更新日期:1990-06-01 00:00:00
abstract::We present a 31-year-old female who had undergone an allogeneic bone marrow transplantation and who was started on intravenous posaconazole for pulmonary mycosis while undergoing continuous venovenous hemofiltration (CVVH). We performed steady-state pharmacokinetic evaluations for both posaconazole and sulfobutylether...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01493-15
更新日期:2015-10-01 00:00:00
abstract::Persistence of Mycobacterium tuberculosis remains a significant challenge for the effective treatment of tuberculosis in humans. In animals that develop necrotic lung lesions following infection with M. tuberculosis, drug-tolerant bacilli are present and persist in an extracellular microenvironment within the necrotic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00217-12
更新日期:2012-06-01 00:00:00
abstract::Anidulafungin concentrations were quantified with high-pressure liquid chromatography (HPLC) and UV detection of the ascites fluid and pleural effusion of 10 adult critically ill patients. Samples were collected from ascites fluid and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulaf...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02326-17
更新日期:2018-03-27 00:00:00
abstract::The aminoglycoside Geneticin (G418) is known to inhibit cell culture proliferation, via virus-specific mechanisms, of two different virus genera from the family Flaviviridae. Here, we tried to determine whether Geneticin can selectively alter the switching of the nucleotide 1 to 570 RNA region of hepatitis C virus (HC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02511-15
更新日期:2015-11-30 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::Cultures of Escherichia coli were exposed to nalidixic acid in an in vitro model in which the conditions of drug-organism interaction resembled those of bacterial cystitis treatment. Results obtained in this way suggested that emergence of bacterial resistance should not be a major problem in treatment of uncomplicate...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.12.6.678
更新日期:1977-12-01 00:00:00