Activity of the histone deacetylase inhibitor FR235222 on Toxoplasma gondii: inhibition of stage conversion of the parasite cyst form and study of new derivative compounds.

Abstract:

:Bradyzoite-to-tachyzoite conversion plays a role in the pathogenesis of recrudescence of ocular toxoplasmosis and disease in immunocompromised persons. The currently available medicines are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. A previous study showed that the histone deacetylase inhibitor FR235222 has a dramatic effect on tachyzoite growth and induces tachyzoite-to-bradyzoite conversion in vitro. The present study shows that FR235222 can target in vitro-converted cysts and bradyzoites. Moreover, the compound is active on ex vivo T. gondii cysts. Free bradyzoites isolated after lysis of the cell wall did not proliferate in vitro when the cyst was treated with FR235222. The results imply that this compound is able to cross the T. gondii cystic cell wall. Fluorescent labeling shows that the compound impairs the capacity of the bradyzoites to convert without damaging the cyst wall integrity. In vivo inoculation of formerly treated cysts fails to infect mice when these cysts were treated with FR235222. We used our structural knowledge of FR235222 and its target, T. gondii HDAC3, to synthesize new FR235222 derivative compounds. We identified two new molecules that are highly active against tachyzoites. They harbor a better selectivity index that is more suitable for a future in vivo approach. These results identify FR235222 and its derivatives as new lead compounds in the range of therapeutics available for acute and chronic toxoplasmosis.

authors

Maubon D,Bougdour A,Wong YS,Brenier-Pinchart MP,Curt A,Hakimi MA,Pelloux H

doi

10.1128/AAC.00462-10

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

4843-50

issue

11

eissn

0066-4804

issn

1098-6596

pii

AAC.00462-10

journal_volume

54

pub_type

杂志文章
  • Generation of stable cell lines expressing Lamivudine-resistant hepatitis B virus for antiviral-compound screening.

    abstract::Lamivudine [beta-L-(-)-2',3'-dideoxy-3'-thiacytidine] is a potent inhibitor of hepadnavirus replication and is used both to treat chronic hepatitis B virus (HBV) infections and to prevent reinfection of transplanted livers. Unfortunately, lamivudine-resistant HBV variants do arise during prolonged therapy, indicating ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.6.1936-1942.2003

    authors: Walters KA,Tipples GA,Allen MI,Condreay LD,Addison WR,Tyrrell L

    更新日期:2003-06-01 00:00:00

  • Fluorometric measurement of ofloxacin uptake by human polymorphonuclear leukocytes.

    abstract::A fluorometric assay, based on the natural fluorescence of the quinolone nucleus, was used to determine the uptake of ofloxacin by human polymorphonuclear leukocytes. The ratio of cellular concentration to extracellular concentration (C/E) at 20 min and 37 degrees C was 7.2, using an extracellular concentration of 5 m...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.33.5.653

    authors: Pascual A,Garcia I,Perea EJ

    更新日期:1989-05-01 00:00:00

  • Drug-induced regulation of the MDR1 promoter in Candida albicans.

    abstract::Resistance of Candida albicans to azole antifungal drugs is mediated by two types of efflux pumps, encoded by the MDR1 gene and the CDR gene family. MDR1 mRNA levels in a susceptible clinical isolate are induced by benomyl (BEN) but not by other drugs previously shown to induce MDR1. To monitor MDR1 expression under s...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.7.2785-2792.2005

    authors: Harry JB,Oliver BG,Song JL,Silver PM,Little JT,Choiniere J,White TC

    更新日期:2005-07-01 00:00:00

  • Biofilms Formed by Isolates from Recurrent Vulvovaginal Candidiasis Patients Are Heterogeneous and Insensitive to Fluconazole.

    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

    doi:10.1128/AAC.01065-17

    authors: Sherry L,Kean R,McKloud E,O'Donnell LE,Metcalfe R,Jones BL,Ramage G

    更新日期:2017-08-24 00:00:00

  • Measurement of voriconazole activity against Candida albicans, C. glabrata, and C. parapsilosis isolates using time-kill methods validated by high-performance liquid chromatography.

    abstract::We developed a high-performance liquid chromatography (HPLC) assay to validate time-kill and postantifungal-effect (PAFE) experiments for voriconazole against Candida albicans, Candida glabrata, and Candida parapsilosis isolates. Voriconazole exerted prolonged fungistatic activity but no PAFE at concentrations achieva...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00308-07

    authors: Li Y,Nguyen MH,Derendorf H,Cheng S,Clancy CJ

    更新日期:2007-08-01 00:00:00

  • Inducement and reversal of tetracycline resistance in Escherichia coli K-12 and expression of proton gradient-dependent multidrug efflux pump genes.

    abstract::Expression of eight transporter genes of Escherichia coli K-12 and its DeltaacrAB mutant prior to and after induction of both strains to tetracycline resistance and after reversal of induced resistance were analyzed by quantitative reverse transcriptase PCR. All transporter genes were overexpressed after induced resis...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.8.3578-3582.2005

    authors: Viveiros M,Jesus A,Brito M,Leandro C,Martins M,Ordway D,Molnar AM,Molnar J,Amaral L

    更新日期:2005-08-01 00:00:00

  • Comparison of the beta-lactamase gene cluster in clonally distinct strains of Enterococcus faecalis.

    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

    authors: Tomayko JF,Zscheck KK,Singh KV,Murray BE

    更新日期:1996-05-01 00:00:00

  • Novel cyclic lipodepsipeptide from Pseudomonas syringae pv. lachrymans strain 508 and syringopeptin antimicrobial activities.

    abstract::The syringopeptins are a group of antimicrobial cyclic lipodepsipeptides produced by several plant-associated pseudomonads. A novel syringopeptin, SP508, was shown to be produced as two homologs (A and B) by Pseudomonas syringae pv. lachrymans strain 508 from apple and to structurally resemble syringopeptin SP22. SP50...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.12.5037-5045.2005

    authors: Grgurina I,Bensaci M,Pocsfalvi G,Mannina L,Cruciani O,Fiore A,Fogliano V,Sorensen KN,Takemoto JY

    更新日期:2005-12-01 00:00:00

  • Relationship of carbapenem restriction in 22 university teaching hospitals to carbapenem use and carbapenem-resistant Pseudomonas aeruginosa.

    abstract::Many hospital antimicrobial stewardship programs restrict the availability of selected drugs by requiring prior approval. Carbapenems may be among the restricted drugs, but it is unclear if hospitals that restrict availability actually use fewer carbapenems than hospitals that do not restrict use. Nor is it clear if r...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究

    doi:10.1128/AAC.01535-08

    authors: Pakyz AL,Oinonen M,Polk RE

    更新日期:2009-05-01 00:00:00

  • Results of German multicenter study of antimicrobial susceptibilities of Trichophyton rubrum and Trichophyton mentagrophytes strains causing tinea unguium. German Collaborative Dermatophyte Drug Susceptibility Study Group.

    abstract::Thirty-two strains of Trichophyton rubrum and 16 strains of Trichophyton mentagrophytes isolated from patients with tinea unguium in various parts of Germany were subjected to a microdilution test with six systemic or topical antimycotic agents. Apart from griseofulvin, there were no species-specific differences betwe...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,多中心研究

    doi:10.1128/aac.39.5.1206

    authors: Korting HC,Ollert M,Abeck D

    更新日期:1995-05-01 00:00:00

  • National Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART).

    abstract::A multicenter collection of bacteremic isolates of Escherichia coli (n = 423), Klebsiella pneumoniae (n = 372), Pseudomonas aeruginosa (n = 300), and Acinetobacter baumannii complex (n = 199) was analyzed for susceptibility. Xpert Carba-R assay and sequencing for mcr genes were performed for carbapenem- or colistin-re...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01089-20

    authors: Liu PY,Lee YL,Lu MC,Shao PL,Lu PL,Chen YH,Cheng SH,Ko WC,Lin CY,Wu TS,Yen MY,Wang LS,Liu CP,Lee WS,Chen YS,Wang FD,Tseng SH,Lin CN,Tang HJ,Chen YH,Sheng WH,Lee CM,Liao MH,Hsueh PR

    更新日期:2020-09-21 00:00:00

  • Modest but variable effect of rifampin on steady-state plasma pharmacokinetics of efavirenz in healthy African-American and Caucasian volunteers.

    abstract::Efavirenz-based antiretroviral regimen is preferred during rifampin-containing tuberculosis therapy. However, current pharmacokinetic data are insufficient to guide optimized concurrent dosing. This study aimed to better characterize the effects of rifampin on efavirenz pharmacokinetics. Subjects were randomized to re...

    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.00980-10

    authors: Kwara A,Tashima KT,Dumond JB,Poethke P,Kurpewski J,Kashuba AD,Court MH,Greenblatt DJ

    更新日期:2011-07-01 00:00:00

  • Interpretive standards for disk susceptibility tests with Sch 21420 and amikacin.

    abstract::Disk susceptibility tests with two structurally related aminoglycosides (amikacin and Sch 21420) were evaluated. Tests with 10- and 30-micrograms amikacin disks confirmed previous recommendations for interpretive zone standards; 30-micrograms disks are preferred. Tests with 10-, 20-, and 30-micrograms Sch 21420 disks ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.18.4.616

    authors: Barry AL,Thornsberry C,Jones RN,Gerlach EH

    更新日期:1980-10-01 00:00:00

  • In vitro synergism observed with azithromycin, clarithromycin, minocycline, or tigecycline in association with antifungal agents against Pythium insidiosum.

    abstract::We describe here the in vitro activities of azithromycin, clarithromycin, minocycline, or tigecycline alone and in combination with amphotericin B, itraconazole, terbinafine, voriconazole, anidulafungin, caspofungin, or micafungin against 30 isolates of the oomycete Pythium insidiosum. The assays were based on the CLS...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02349-14

    authors: Jesus FP,Ferreiro L,Loreto ÉS,Pilotto MB,Ludwig A,Bizzi K,Tondolo JS,Zanette RA,Alves SH,Santurio JM

    更新日期:2014-09-01 00:00:00

  • Precision and accuracy of fluconazole susceptibility testing by broth microdilution, Etest, and disk diffusion methods.

    abstract::Interpretive agreements among the results of fluconazole broth microdilution tests, Etests, and disk diffusion tests were documented by evaluating 495 Candida spp. Microdilution reference test results were in agreement with 96% of the Etest results; most discrepancies were minor differences. Fluconazole resistance of ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.6.1781-1784.2002

    authors: Barry AL,Pfaller MA,Rennie RP,Fuchs PC,Brown SD

    更新日期:2002-06-01 00:00:00

  • Hydrophilicity of quinolones is not an exclusive factor for decreased activity in efflux-mediated resistant mutants of Staphylococcus aureus.

    abstract::The elevated expression of the norA gene is responsible for efflux-mediated resistance to quinolones in Staphylococcus aureus (E.Y.W. Ng, M. Trucksis, and D.C. Hooper, Antimicrob. Agents Chemother. 38:1345-1355, 1994). For S. aureus transformed with a plasmid containing the cloned norA gene, SA113(pTUS20) (H. Yoshida,...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.8.1835

    authors: Takenouchi T,Tabata F,Iwata Y,Hanzawa H,Sugawara M,Ohya S

    更新日期:1996-08-01 00:00:00

  • Population Pharmacokinetics of Tafenoquine, a Novel Antimalarial.

    abstract::Tafenoquine is a novel 8-aminoquinoline antimalarial drug recently approved by the U.S. Food and Drug Administration (FDA) for the radical cure of acute Plasmodium vivax malaria, which is the first new treatment in almost 60 years. A population pharmacokinetic (POP PK) analysis was conducted with tafenoquine exposure ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00711-18

    authors: Thakkar N,Green JA,Koh GCKW,Duparc S,Tenero D,Goyal N

    更新日期:2018-10-24 00:00:00

  • Streptomycin resistance in mycobacteria.

    abstract::Streptomycin, the first antibiotic used in tuberculosis control programs, perturbs protein synthesis at the ribosome level. It is shown here that streptomycin resistance in some clinical isolates of Mycobacterium tuberculosis is associated either with missense mutations in the rpsL gene, which encodes ribosomal protei...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.2.238

    authors: Honoré N,Cole ST

    更新日期:1994-02-01 00:00:00

  • Importance of the genetic diversity within the Mycobacterium tuberculosis complex for the development of novel antibiotics and diagnostic tests of drug resistance.

    abstract::Despite being genetically monomorphic, the limited genetic diversity within the Mycobacterium tuberculosis complex (MTBC) has practical consequences for molecular methods for drug susceptibility testing and for the use of current antibiotics and those in clinical trials. It renders some representatives of MTBC intrins...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,评审

    doi:10.1128/AAC.01641-12

    authors: Köser CU,Feuerriegel S,Summers DK,Archer JA,Niemann S

    更新日期:2012-12-01 00:00:00

  • Overproduction of a penicillin-binding protein is not the only mechanism of penicillin resistance in Enterococcus faecium.

    abstract::In 1989 and 1990, a large number of ampicillin-resistant strains of Enterococcus faecium were isolated from infected patients treated at intensive care units in Berlin, Germany. Twenty-five clinical isolates, including five different biotypes as classified by acid production from various sugars and a wide range of sus...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.4.783

    authors: Klare I,Rodloff AC,Wagner J,Witte W,Hakenbeck R

    更新日期:1992-04-01 00:00:00

  • Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro.

    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

    authors: Yokota T,Konno K,Chonan E,Mochizuki S,Kojima K,Shigeta S,de Clercq E

    更新日期:1990-07-01 00:00:00

  • Mannopeptimycins, new cyclic glycopeptide antibiotics produced by Streptomyces hygroscopicus LL-AC98: antibacterial and mechanistic activities.

    abstract::Mannopeptimycins alpha, beta, gamma, delta, and epsilon are new cyclic glycopeptide antibiotics produced by Streptomyces hygroscopicus LL-AC98. Mannopeptimycins gamma, delta, and epsilon, which have an isovaleryl substitution at various positions on the terminal mannose of the disaccharide moiety, demonstrated moderat...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.1.62-69.2003

    authors: Singh MP,Petersen PJ,Weiss WJ,Janso JE,Luckman SW,Lenoy EB,Bradford PA,Testa RT,Greenstein M

    更新日期:2003-01-01 00:00:00

  • Structure of the Enterovirus 71 3C Protease in Complex with NK-1.8k and Indications for the Development of Antienterovirus Protease Inhibitor.

    abstract::Hand-foot-and-mouth disease (HFMD), caused by enterovirus, is a threat to public health worldwide. To date, enterovirus 71 (EV71) has been one of the major causative agents of HFMD in the Pacific-Asia region, and outbreaks with EV71 cause millions of infections. However, no drug is currently available for clinical the...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00298-17

    authors: Wang Y,Cao L,Zhai Y,Yin Z,Sun Y,Shang L

    更新日期:2017-06-27 00:00:00

  • Concentrations of gatifloxacin in plasma and urine and penetration into prostatic and seminal fluid, ejaculate, and sperm cells after single oral administrations of 400 milligrams to volunteers.

    abstract::Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.45.1.293-297.2001

    authors: Naber CK,Steghafner M,Kinzig-Schippers M,Sauber C,Sörgel F,Stahlberg HJ,Naber KG

    更新日期:2001-01-01 00:00:00

  • Two novel antibiotic resistance genes, tet(44) and ant(6)-Ib, are located within a transferable pathogenicity island in Campylobacter fetus subsp. fetus.

    abstract::New tetracycline and streptomycin resistance genes, tet(44) and ant(6)-Ib, were identified in Campylobacter fetus subsp. fetus within a transferable pathogenicity island that is typically unique to Campylobacter fetus subsp. venerealis. The 640-amino-acid tetracycline resistance determinant, Tet 44, belongs to a class...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00304-10

    authors: Abril C,Brodard I,Perreten V

    更新日期:2010-07-01 00:00:00

  • Outcomes of moderate-to-severe Pneumocystis pneumonia treated with adjunctive steroid in non-HIV-infected patients.

    abstract::While it is well-known that adjunctive corticosteroid use improves the outcome of moderate-to-severe Pneumocystis jirovecii pneumonia (PcP) in patients with human immunodeficiency virus (HIV), there are limited data on its efficacy in non-HIV-infected patients with PcP. Patients undergoing fiber-optic bronchoscopy wit...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00669-11

    authors: Moon SM,Kim T,Sung H,Kim MN,Kim SH,Choi SH,Jeong JY,Woo JH,Kim YS,Lee SO

    更新日期:2011-10-01 00:00:00

  • Mechanism of enhanced activity of liposome-entrapped aminoglycosides against resistant strains of Pseudomonas aeruginosa.

    abstract::Pseudomonas aeruginosa is inherently resistant to most conventional antibiotics. The mechanism of resistance of this bacterium is mainly associated with the low permeability of its outer membrane to these agents. We sought to assess the bactericidal efficacy of liposome-entrapped aminoglycosides against resistant clin...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01547-05

    authors: Mugabe C,Halwani M,Azghani AO,Lafrenie RM,Omri A

    更新日期:2006-06-01 00:00:00

  • Efficacy of NZ2114, a novel plectasin-derived cationic antimicrobial peptide antibiotic, in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

    abstract::Cationic antimicrobial peptides (CAPs) play important roles in host immune defenses. Plectasin is a defensin-like CAP isolated from the saprophytic fungus Pseudoplectania nigrella. NZ2114 is a novel variant of plectasin with potent activity against Gram-positive bacteria. In this study, we investigated (i) the in vivo...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00453-11

    authors: Xiong YQ,Hady WA,Deslandes A,Rey A,Fraisse L,Kristensen HH,Yeaman MR,Bayer AS

    更新日期:2011-11-01 00:00:00

  • Influence of plasma exchange pheresis on plasma elimination of ceftriaxone.

    abstract::The plasma elimination rates of serial 2-g intravenous injections of ceftriaxone were studied in a patient who also was treated with therapeutic plasma exchange pheresis. Plasmapheresis had negligible influence on the total clearance of ceftriaxone. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.6.1276

    authors: Bakken JS,Cavalieri SJ,Gangeness D

    更新日期:1990-06-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of once-daily administration of intravenous tobramycin in adult patients with cystic fibrosis hospitalized for an acute pulmonary exacerbation.

    abstract::The serum pharmacokinetic profile of intravenous (i.v.) tobramycin administration was characterized for a sample of nine adult patients with cystic fibrosis (CF) who were hospitalized for an acute pulmonary exacerbation. Current recommended i.v. tobramycin dosing protocols are predicted through modeling and simulation...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/AAC.00539-13

    authors: Butterfield JM,Lodise TP,Beegle S,Rosen J,Farkas J,Pai MP

    更新日期:2013-10-01 00:00:00