Determinants of Antibacterial Spectrum and Resistance Potential of the Elongation Factor G Inhibitor Argyrin B in Key Gram-Negative Pathogens.


:Argyrins are natural products with antibacterial activity against Gram-negative pathogens, such as Pseudomonas aeruginosa, Burkholderia multivorans, and Stenotrophomonas maltophilia We previously showed that argyrin B targets elongation factor G (FusA). Here, we show that argyrin B activity against P. aeruginosa PAO1 (MIC = 8 μg/ml) was not affected by deletion of the MexAB-OprM, MexXY-OprM, MexCD-OprJ, or MexEF-OprN efflux pump. However, argyrin B induced expression of MexXY, causing slight but reproducible antagonism with the MexXY substrate antibiotic ciprofloxacin. Argyrin B activity against Escherichia coli increased in a strain with nine tolC efflux pump partner genes deleted. Complementation experiments showed that argyrin was effluxed by AcrAB, AcrEF, and MdtFX. Argyrin B was inactive against Acinetobacter baumannii Differences between A. baumannii and P. aeruginosa FusA proteins at key residues for argyrin B interaction implied that natural target sequence variation impacted antibacterial activity. Consistent with this, expression of the sensitive P. aeruginosa FusA1 protein in A. baumannii conferred argyrin susceptibility, whereas resistant variants did not. Argyrin B was active against S. maltophilia (MIC = 4 μg/ml). Spontaneous resistance occurred at high frequency in the bacterium (circa 10-7), mediated by mutational inactivation of fusA1 rather than by amino acid substitutions in the target binding region. This strongly suggested that resistance occurred at high frequency through loss of the sensitive FusA1, leaving an alternate argyrin-insensitive elongation factor. Supporting this, an additional fusA-like gene (fusA2) is present in S. maltophilia that was strongly upregulated in response to mutational loss of fusA1.


Jones AK,Woods AL,Takeoka KT,Shen X,Wei JR,Caughlan RE,Dean CR




Has Abstract


2017-03-24 00:00:00












  • Accelerated denaturation of hemoglobin and the antimalarial action of chloroquine.

    abstract::To study the antimalarial action of chloroquine, normal mouse erythrocytes were used as surrogates for erythrocytoid bodies. These bodies form in the endosomes of intraerythrocytic malaria parasites as they feed on their host and consist of erythrocyte cytoplasm enclosed in a vestige of the erythrocyte membrane. In su...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Fitch CD,Russell NV

    更新日期:2006-07-01 00:00:00

  • IMP dehydrogenase from the protozoan parasite Toxoplasma gondii.

    abstract::The opportunistic apicomplexan parasite Toxoplasma gondii damages fetuses in utero and threatens immunocompromised individuals. The toxicity associated with standard antitoxoplasmal therapies, which target the folate pathway, underscores the importance of examining alternative pharmacological strategies. Parasitic pro...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Sullivan WJ Jr,Dixon SE,Li C,Striepen B,Queener SF

    更新日期:2005-06-01 00:00:00

  • Sensitivity of Candida albicans germ tubes and biofilms to photofrin-mediated phototoxicity.

    abstract::Treatment of mucocutaneous and cutaneous Candida albicans infections with photosensitizing agents and light, termed photodynamic therapy (PDT), offers an alternative to conventional treatments. Initial studies using the clinically approved photosensitizer Photofrin demonstrated the susceptibility of C. albicans to its...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Chabrier-Roselló Y,Foster TH,Pérez-Nazario N,Mitra S,Haidaris CG

    更新日期:2005-10-01 00:00:00

  • Efficacy of ampicillin plus ceftriaxone in treatment of experimental endocarditis due to Enterococcus faecalis strains highly resistant to aminoglycosides.

    abstract::The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the tre...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Gavaldà J,Torres C,Tenorio C,López P,Zaragoza M,Capdevila JA,Almirante B,Ruiz F,Borrell N,Gomis X,Pigrau C,Baquero F,Pahissa A

    更新日期:1999-03-01 00:00:00

  • Activity of telithromycin (HMR 3647) against anaerobic bacteria compared to those of eight other agents by time-kill methodology.

    abstract::Time-kill studies examined the activities of telithromycin (HMR 3647), erythromycin A, azithromycin, clarithromycin, roxithromycin, clindamycin, pristinamycin, amoxicillin-clavulanate, and metronidazole against 11 gram-positive and gram-negative anaerobic bacteria. Time-kill studies were carried out with the addition ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Credito KL,Ednie LM,Jacobs MR,Appelbaum PC

    更新日期:1999-08-01 00:00:00

  • Biomarker-assisted dose selection for safety and efficacy in early development of PNU-100480 for tuberculosis.

    abstract::Tuberculosis is a serious global health threat for which new treatments are urgently needed. This study examined the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of the oxazolidinone PNU-100480 in healthy volunteers, using biomarkers for safety and efficacy. Subjects were ra...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,随机对照试验


    authors: Wallis RS,Jakubiec W,Kumar V,Bedarida G,Silvia A,Paige D,Zhu T,Mitton-Fry M,Ladutko L,Campbell S,Miller PF

    更新日期:2011-02-01 00:00:00

  • Activity of cefepime against ceftazidime- and cefotaxime-resistant gram-negative bacteria and its relationship to beta-lactamase levels.

    abstract::One hundred clinical isolates resistant to ceftazidime and/or cefotaxime were examined for susceptibility to cefepime. The most frequently encountered ceftazidime-cefotaxime-resistant strains belonged to the genera Enterobacter, Pseudomonas, and Citrobacter. Among these strains, 92% were resistant to cefoperazone, 91%...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Fung-Tomc J,Dougherty TJ,DeOrio FJ,Simich-Jacobson V,Kessler RE

    更新日期:1989-04-01 00:00:00

  • Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community.

    abstract::With the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, in which multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Adamowicz EM,Harcombe WR

    更新日期:2020-10-20 00:00:00

  • Liposomal amphotericin B inhibits in vitro T-lymphocyte response to antigen.

    abstract::The effects of free amphotericin B (as Fungizone) and amphotericin B (AMB) incorporated into liposomes on the proliferation of lymphocytes were determined. Freshly obtained guinea pig and rat antigen-specific lymphocytes were compared with rat T-lymphocyte cell lines cultured for a long period of time. Incorporation o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Boggs JM,Chang NH,Goundalkar A

    更新日期:1991-05-01 00:00:00

  • Crystal structures of biapenem and tebipenem complexed with penicillin-binding proteins 2X and 1A from Streptococcus pneumoniae.

    abstract::Biapenem is a parenteral carbapenem antibiotic that exhibits wide-ranging antibacterial activity, remarkable chemical stability, and extensive stability against human renal dehydropeptidase-I. Tebipenem is the active form of tebipenem pivoxil, a novel oral carbapenem antibiotic that has a high level of bioavailability...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Yamada M,Watanabe T,Baba N,Takeuchi Y,Ohsawa F,Gomi S

    更新日期:2008-06-01 00:00:00

  • Scanning electron microscopy of the H37Ra strain of Mycobacterium tuberculosis exposed to isoniazid.

    abstract::The morphology of cells of the H37Ra strain of Mycobacterium tuberculosis exposed to 0.5 mug of isonicotinic acid hydrazide (isoniazid) per ml was examined by scanning electron microscopy (SEM). Cells that were exposed to isoniazid for 3 h showed no detectable change, whereas cells exposed to the drug for 24 h exhibit...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Takayama K,Wang L,Merkal RS

    更新日期:1973-07-01 00:00:00

  • Rifampin reduces concentrations of trimethoprim and sulfamethoxazole in serum in human immunodeficiency virus-infected patients.

    abstract::To determine whether rifampin reduces concentrations of trimethoprim (TMP) and sulfamethoxazole (SMX) in serum of human immunodeficiency virus (HIV)-infected persons, levels of these agents were determined by high-performance liquid chromatography before and after more than 12 days of standard antituberculosis treatme...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章


    authors: Ribera E,Pou L,Fernandez-Sola A,Campos F,Lopez RM,Ocaña I,Ruiz I,Pahissa A

    更新日期:2001-11-01 00:00:00

  • Therapeutic drug monitoring of posaconazole in hematology patients: experience with a new high-performance liquid chromatography-based method.

    abstract::Parallel administration of the proton pump inhibitor (PPI) esomeprazole has been shown to decrease oral bioavailability of posaconazole in healthy volunteers. We prospectively analyzed serum samples (n = 59) obtained from hematology patients (n = 27) under posaconazole prophylaxis. Patients treated concomitantly with ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Neubauer WC,Engelhardt M,König A,Hieke S,Jung M,Bertz H,Kümmerer K

    更新日期:2010-09-01 00:00:00

  • Plasmid-determined resistance to boron and chromium compounds in Pseudomonas aeruginosa.

    abstract::Plasmids determining resistance to arsenic, mercury, silver, and tellurium compounds in Escherichia coli and Pseudomonas aeruginosa were tested for resistance to 40 other metal compounds. Resistance to trivalent boron and hexavalent chromium compounds was a property of certain P. aeruginosa plasmids. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Summers AO,Jacoby GA

    更新日期:1978-04-01 00:00:00

  • Determination of zidovudine triphosphate intracellular concentrations in peripheral blood mononuclear cells from human immunodeficiency virus-infected individuals by tandem mass spectrometry.

    abstract::Nucleoside reverse transcriptase inhibitors (NRTIs) used against the human immunodeficiency virus (HIV) need to be activated intracellularly to their triphosphate moiety to inhibit HIV replication. Intracellular concentrations of these NRTI triphosphates, especially zidovudine triphosphate (ZDV-TP), are relatively low...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章


    authors: Font E,Rosario O,Santana J,García H,Sommadossi JP,Rodriguez JF

    更新日期:1999-12-01 00:00:00

  • R-factor carriage in a group F vibrio isolated from Bangladesh.

    abstract::Two group F vibrio organisms have been identified among a collection of vibrio strains isolated from the aquatic environment in Bangladesh. Neither group F strain produced a cholera-like enterotoxin. One of the isolates, BV12, contained an R plasmid conferring resistance to streptomycin and chloramphenicol. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: McNicol LA,Kaper JB,Lockman HA,Remmers EF,Spira WM,Colwell RR

    更新日期:1980-03-01 00:00:00

  • New schedule for tobramycin administration.

    abstract::Ten patients received a loading dose of tobramycin of 60 mg/m2 intravenously over 0.5 h followed immediately by 60 mg/m2 over 2 h every 4 h. The highest mean serum concentration (at the end of the loading dose) was 6.0 +/- 0.3 microgram/ml (range, 3.2 to 10.9 microgram/ml). The mean serum concentration 2 h after the e...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Lawson RD,Bodey GP,Pan T,Smith TL

    更新日期:1980-05-01 00:00:00

  • CMCdG, a Novel Nucleoside Analog with Favorable Safety Features, Exerts Potent Activity against Wild-Type and Entecavir-Resistant Hepatitis B Virus.

    abstract::We designed, synthesized, and characterized a novel nucleoside analog, (1S,3S,5S)-3-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-5-hydroxy-1-(hydroxymethyl)-2-methylene-cyclopentanecarbonitrile, or 4'-cyano-methylenecarbocyclic-2'-deoxyguanosine (CMCdG), and evaluated its anti-hepatitis B virus (anti-HBV) activity, safet...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Higashi-Kuwata N,Hayashi S,Das D,Kohgo S,Murakami S,Hattori SI,Imoto S,Venzon DJ,Singh K,Sarafianos SG,Tanaka Y,Mitsuya H

    更新日期:2019-03-27 00:00:00

  • Resistance caused by decreased penetration of beta-lactam antibiotics into Enterobacter cloacae.

    abstract::Strains of Enterobacter cloacae were selected on the basis of resistance to aztreonam, ceftazidime, moxalactam, or imipenem. All strains produced the same E2 beta-lactamase, with an isoelectric point greater than 9.5 and with high hydrolytic activity in the presence of cephaloridine. Resistance to beta-lactams could n...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Bush K,Tanaka SK,Bonner DP,Sykes RB

    更新日期:1985-04-01 00:00:00

  • Chloramphenicol acetyltransferases specified by fi minus R factors.

    abstract::Chloramphenicol acetyltransferases specified by fi(-) (F fertility-noninhibiting) R factors were compared with those specified by the fi(+) R factors R1, 222, and R6-S. Three classes of enzyme were distinguished: class I was determined by group N fi(-) R factors and was indistinguishable from the enzyme determined by ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Foster TJ,Shaw WV

    更新日期:1973-01-01 00:00:00

  • Mechanisms involved in the selection of HIV-1 reverse transcriptase thumb subdomain polymorphisms associated with nucleoside analogue therapy failure.

    abstract::Previous studies showed an increased prevalence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) thumb subdomain polymorphisms Pro272, Arg277, and Thr286 in patients failing therapy with nucleoside analogue combinations. Interestingly, wild-type HIV-1(BH10) RT contains Pro272, Arg277, and Thr2...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Betancor G,Puertas MC,Nevot M,Garriga C,Martínez MA,Martinez-Picado J,Menéndez-Arias L

    更新日期:2010-11-01 00:00:00

  • Efficacy of ciprofloxacin for experimental endocarditis caused by methicillin-susceptible or -resistant strains of Staphylococcus aureus.

    abstract::The efficacy of ciprofloxacin for experimental aortic valve endocarditis in rabbits infected by either a methicillin-susceptible or a methicillin-resistant strain of Staphylococcus aureus was compared with standard therapy of nafcillin or vancomycin, respectively. After 4 days of therapy, ciprofloxacin reduced the cou...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Carpenter TC,Hackbarth CJ,Chambers HF,Sande MA

    更新日期:1986-09-01 00:00:00

  • Mode of action of a new type of UDP-glucose analog against herpesvirus replication.

    abstract::The mode of action of a new type of UDP-glucose analog against herpes simplex virus type 1 (HSV-1) replication was examined. The analog showed good selectivity and potent activity. At 10 micrograms/ml, P-536 inhibited the formation of infectious HSV-1 by more than 90%, whereas at 100 micrograms/ml it had no cytotoxic ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Alarcón B,González ME,Carrasco L,Méndez-Castrillón PP,García-López MT,de las Heras FG

    更新日期:1988-08-01 00:00:00

  • Novel Zinc-Attenuating Compounds as Potent Broad-Spectrum Antifungal Agents with In Vitro and In Vivo Efficacy.

    abstract::An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here we report the identification and characterization of two novel zinc-attenuating compounds, Z...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Cohrt KAO,Marín L,Kjellerup L,Clausen JD,Dalby-Brown W,Calera JA,Winther AL

    更新日期:2018-04-26 00:00:00

  • Human salivary mucin MUC7 12-mer-L and 12-mer-D peptides: antifungal activity in saliva, enhancement of activity with protease inhibitor cocktail or EDTA, and cytotoxicity to human cells.

    abstract::MUC7 12-mer-L exhibits potent in vitro antifungal activity in low-ionic-strength buffers. In this study, we investigated the anticandidal activity and stability of MUC7 12-mer-L and its all-D-amino-acid isomer, along with Hsn5 12-mer (P113) and magainin-II, in human clarified and unclarified saliva in the absence or p...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Wei GX,Bobek LA

    更新日期:2005-06-01 00:00:00

  • Class 1 integron-borne gene cassettes in multidrug-resistant Yersinia enterocolitica strains of different phenotypic and genetic types.

    abstract::Seventy nine strains of Yersinia enterocolitica resistant to one or more antimicrobials were analyzed for integrons. Only class 1 sul1 integrons containing aadA1a (28 strains), aadA1a-dfr1-sat1 (2 strains), and dfr1-aadA1a (1 strain) gene cassettes were found. The first two types were found in clinical isolates belong...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Soto SM,Lobato MJ,Mendoza MC

    更新日期:2003-01-01 00:00:00

  • Heterocycle Thiazole Compounds Exhibit Antifungal Activity through Increase in the Production of Reactive Oxygen Species in the Cryptococcus neoformans-Cryptococcus gattii Species Complex.

    abstract::Human cryptococcosis can occur as a primary or opportunistic infection and develops as an acute, subacute, or chronic systemic infection involving different organs of the host. Given the limited therapeutic options and the occasional resistance to fluconazole, there is a need to develop novel drugs for the treatment o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Sá NP,Lima CM,Lino CI,Barbeira PJS,Baltazar LM,Santos DA,Oliveira RB,Mylonakis E,Fuchs BB,Johann S

    更新日期:2017-07-25 00:00:00

  • Streptococcus pneumoniae transposon Tn1545/Tn6003 changes to Tn6002 due to spontaneous excision in circular form of the erm(B)- and aphA3-containing macrolide-aminoglycoside-streptothricin (MAS) element.

    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

    pub_type: 杂志文章


    authors: Palmieri C,Mingoia M,Massidda O,Giovanetti E,Varaldo PE

    更新日期:2012-11-01 00:00:00

  • Identification of the coumermycin A(1) biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489.

    abstract::The biosynthetic gene cluster of the aminocoumarin antibiotic coumermycin A(1) was cloned by screening of a cosmid library of Streptomyces rishiriensis DSM 40489 with heterologous probes from a dTDP-glucose 4,6-dehydratase gene, involved in deoxysugar biosynthesis, and from the aminocoumarin resistance gyrase gene gyr...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Wang ZX,Li SM,Heide L

    更新日期:2000-11-01 00:00:00

  • In Vitro Activity of Ceftazidime-Avibactam against Contemporary Pseudomonas aeruginosa Isolates from U.S. Medical Centers by Census Region, 2014.

    abstract::Thein vitroantibacterial activities of ceftazidime-avibactam and comparator agents were evaluated using reference broth microdilution methods against 1,743Pseudomonas aeruginosaisolates collected in 2014 from 69 U.S. medical centers, representing each of the nine census regions. Ceftazidime-avibactam demonstrated pote...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章


    authors: Huband MD,Castanheira M,Flamm RK,Farrell DJ,Jones RN,Sader HS

    更新日期:2016-03-25 00:00:00