Inhibition of Pneumocystis carinii dihydropteroate synthetase by para-acetamidobenzoic acid: possible mechanism of action of isoprinosine in human immunodeficiency virus infection.

Abstract:

:Isoprinosine has been reported to decrease progression to AIDS, primarily by preventing Pneumocystis carinii pneumonia (PCP), in human immunodeficiency virus-infected patients, but the mechanism of action is unknown. para-Acetamidobenzoic acid (PAcBA), one component of isoprinosine, is structurally related to para-aminobenzoic acid (PABA), a precursor of de novo folate synthesis. This pathway is known to be important for P. carinii because sulfonamides, which are effective anti-P. carinii agents, inhibit incorporation of PABA into folate precursors by the enzyme dihydropteroate synthetase (DHPS). Inhibition of P. carinii DHPS by PAcBA was investigated by using two assays. In short-term cultures of P. carinii from rats, [3H]PABA incorporation into reduced folates was inhibited by both isoprinosine (mean +/- standard error 50% inhibitory concentration [IC50], 20 +/- 8.4 microM) and PAcBA free acid (IC50, 240 +/- 100 microM); a soluble PAcBA salt was more potent than PAcBA free acid alone (IC50, 29 +/- 48 microM). The activity of PAcBA free acid was confirmed in a cell-free DHPS inhibition assay (IC50, 120 +/- 120 microM). Inosine and dimethylaminopropanol, two other components of isoprinosine, were poor inhibitors of PABA incorporation (IC50, > 1,000 microM). PAcBA free acid also showed activity in inhibiting the DHPS of Toxoplasma gondii, but was a poor inhibitor of the DHPSs of Escherichia coli and Saccharomyces cerevisiae. In a rat model of PCP, the PAcBA salt administered intraperitoneally demonstrated no activity against established PCP either alone or when used in combination with trimethoprim; the lack of efficacy in this model may be due to the rapid metabolism of the drug. Prevention of PCP by PaCBA through inhibition of P. carinii DHPS may explain the activity of isoprinosine in decreasing the progression to AIDS in human immunodeficiency virus-infected patients.

authors

Kovacs JA,Powell F,Voeller D,Allegra CJ

doi

10.1128/aac.37.6.1227

subject

Has Abstract

pub_date

1993-06-01 00:00:00

pages

1227-31

issue

6

eissn

0066-4804

issn

1098-6596

journal_volume

37

pub_type

杂志文章
  • Pleiotropic antibiotic resistance mutations associated with ribosomes and ribosomal subunits in Mycobacterium smegmatis.

    abstract::Viomycin-resistant strains isolated from Mycobacterium smegmatis demonstrated pleiotropic resistance to tuberactinomycin-N, capreomycin, streptomycin, and kanamycin as a result of mutational alteration of ribosomes, even though they were selected for resistance to a single antibiotic. The pleiotropic drug resistance o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.6.1.46

    authors: Yamada T,Masuda K,Shoji K,Hori M

    更新日期:1974-07-01 00:00:00

  • In vitro antifungal susceptibilities of Trichosporon species.

    abstract::The in vitro activities of amphotericin B, itraconazole, fluconazole, voriconazole, posaconazole, and ravuconazole against 39 isolates of Trichosporon spp. were determined by the NCCLS M27-A microdilution method. The azoles tested appeared to be more potent than amphotericin B. Low minimal fungicidal concentration/MIC...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.4.1144-1146.2002

    authors: Paphitou NI,Ostrosky-Zeichner L,Paetznick VL,Rodriguez JR,Chen E,Rex JH

    更新日期:2002-04-01 00:00:00

  • Potent cephalosporinase inhibitors: 7 beta-[2-(1, 3-dithiolan-2-ylidene) acetamido] cephalosporins and related compounds.

    abstract::Cephalosporins possessing a 1, 3-dithiolane, 1, 3-dithiane, or 1, 3-dithietane ring on their 7 beta-substituents showed potent inhibitory activity against cephaloridine hydrolysis by cephalosporinases purified from proteus morganii, Proteus rettgeri, and Proteus inconstans, which were not inhibited by clavulanic acid,...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.21.4.613

    authors: Ohya S,Miyadera T,Yamazaki M

    更新日期:1982-04-01 00:00:00

  • New rapid assay for nafcillin in serum by spectrofluorometry.

    abstract::A new, rapid method for measuring serum levels of nafcillin by spectrofluorometry is described. The method involves extraction of 2 ml of acidified serum with n-butyl chloride, subjecting the organic solvent layer to excitation at 340 nm, and measuring the relative intensity of emission fluorescence at 380 nm. An exce...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.16.2.210

    authors: Lichtenwalner DM,Suh B,Lorber B,Sugar AM

    更新日期:1979-08-01 00:00:00

  • Emergence and Distribution of Plasmids Bearing the blaOXA-51-like gene with an upstream ISAba1 in carbapenem-resistant Acinetobacter baumannii isolates in Taiwan.

    abstract::The bla(OXA-51)-like gene with an upstream ISAba1 (ISAba1-bla(OXA-51)-like gene) was originally found on the chromosomes of carbapenem-resistant or -susceptible Acinetobacter baumannii isolates. However, a plasmid-borne ISAba1-bla(OXA-51)-like gene has recently been identified in Acinetobacter genomic species 13TU and...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00764-10

    authors: Chen TL,Lee YT,Kuo SC,Hsueh PR,Chang FY,Siu LK,Ko WC,Fung CP

    更新日期:2010-11-01 00:00:00

  • Antimicrobial activities of piperacillin-tazobactam against Haemophilus influenzae isolates, including beta-lactamase-negative ampicillin-resistant and beta-lactamase-positive amoxicillin-clavulanate-resistant isolates, and mutations in their quinolone re

    abstract::Beta-lactamase-negative ampicillin-resistant (BLNAR) isolates of Haemophilus influenzae have been emerging in some countries, including Japan. The Clinical and Laboratory Standards Institute has only a susceptible MIC breakpoint (< or = 1 microg/ml) for piperacillin-tazobactam and a disclaimer comment that BLNAR H. in...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00192-09

    authors: Hirakata Y,Ohmori K,Mikuriya M,Saika T,Matsuzaki K,Hasegawa M,Hatta M,Yamamoto N,Kunishima H,Yano H,Kitagawa M,Arai K,Kawakami K,Kobayashi I,Jones RN,Kohno S,Yamaguchi K,Kaku M

    更新日期:2009-10-01 00:00:00

  • Inhibition of ribonucleic acid polymerase by a bacteriocin from Bacteroides fragilis.

    abstract::The Bacteroides fragilis bacteriocin which inhibits ribonucleic acid (RNA) polymerase activity had a narrow activity spectrum in vivo and only inhibited the growth of certain B. fragilis strains. In vitro the bacteriocin was not specific and inhibited RNA polymerases from widely diverse bacterial genera. RNA polymeras...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.20.4.437

    authors: Mossie KG,Robb FT,Jones DT,Woods DR

    更新日期:1981-10-01 00:00:00

  • Antibacterial activity of a competence-stimulating peptide in experimental sepsis caused by Streptococcus pneumoniae.

    abstract::Streptococcus pneumoniae, a major cause of human disease, produces a 17-mer autoinducer peptide pheromone (competence-stimulating peptide [CSP]) for the control of competence for genetic transformation. Due to previous work linking CSP to stress phenotypes, we set up an in vivo sepsis model to assay its effect on viru...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.12.4725-4732.2004

    authors: Oggioni MR,Iannelli F,Ricci S,Chiavolini D,Parigi R,Trappetti C,Claverys JP,Pozzi G

    更新日期:2004-12-01 00:00:00

  • A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

    abstract::The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patien...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03796-14

    authors: Ternavasio-de la Vega HG,Mateos-Díaz AM,Martinez JA,Almela M,Cobos-Trigueros N,Morata L,De-la-Calle C,Sala M,Mensa J,Marcos M,Soriano A

    更新日期:2014-12-01 00:00:00

  • Evaluation of a new line probe assay for rapid identification of gyrA mutations in Mycobacterium tuberculosis.

    abstract::Resistance of Mycobacterium tuberculosis to fluoroquinolones (FQ) results mostly from mutations in the gyrA gene. We developed a reverse hybridization-based line probe assay in which oligonucleotide probes carrying the wild-type gyrA sequence, a serine-to-threonine (S95T) polymorphism, and gyrA mutations (A90V, A90V-S...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.49.7.2928-2933.2005

    authors: Giannoni F,Iona E,Sementilli F,Brunori L,Pardini M,Migliori GB,Orefici G,Fattorini L

    更新日期:2005-07-01 00:00:00

  • Selective interaction of the human immunodeficiency virus type 1 reverse transcriptase nonnucleoside inhibitor efavirenz and its thio-substituted analog with different enzyme-substrate complexes.

    abstract::Accumulating data have brought the nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) into the forefront of antiretroviral therapy. Among the emerging compounds in this class, a particularly attractive one is efavirenz (Sustiva), recently approved for clinical use by the U.S. Food and Drug Administration. In...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.5.1186-1194.2000

    authors: Maga G,Ubiali D,Salvetti R,Pregnolato M,Spadari S

    更新日期:2000-05-01 00:00:00

  • Pharmacokinetics of clarithromycin and zidovudine in patients with AIDS.

    abstract::The interrelationships between the pharmacokinetics of zidovudine alone and of zidovudine plus clarithromycin were evaluated with 18 volunteers with AIDS who had no infection with Mycobacterium avium complex or clinical evidence of gastroenteritis. Patients received 200 mg of zidovudine orally every 8 h on days 1 to 4...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/aac.39.6.1355

    authors: Vance E,Watson-Bitar M,Gustavson L,Kazanjian P

    更新日期:1995-06-01 00:00:00

  • Characterization of rpsL and rrs mutations in streptomycin-resistant Mycobacterium tuberculosis isolates from diverse geographic localities.

    abstract::Two genes (rpsL and rrs) with mutations associated with streptomycin resistance in Mycobacterium tuberculosis were characterized in 78 streptomycin-resistant and 61 streptomycin-susceptible isolates recovered from patients living in the United States, South America, Europe, Africa, and Asia. Fifty-four percent of the ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.4.1024

    authors: Sreevatsan S,Pan X,Stockbauer KE,Williams DL,Kreiswirth BN,Musser JM

    更新日期:1996-04-01 00:00:00

  • Susceptibility testing of bacteria recovered from patients with peritonitis complicating continuous ambulatory peritoneal dialysis.

    abstract::Antagonism of antibiotic activity by peritoneal dialysate has been postulated to be a cause of failure of treatment of peritonitis complicating continuous ambulatory peritoneal dialysis. We evaluated by a case-control study whether unexpected treatment failure could be attributed to such antagonism. Bacteria isolated ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.5.1097

    authors: Ludlam H,Johnston L,Hopkins P

    更新日期:1992-05-01 00:00:00

  • Use of molecular beacons to detect an antifolate resistance-associated mutation in Plasmodium falciparum.

    abstract::A PCR-based technique using new fluorescent probes, called molecular beacons, was developed to detect the antifolate resistance-associated S108N point mutation in Plasmodium falciparum. One hundred African clinical isolates were tested by the new method in comparison with the PCR-restriction fragment length polymorphi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.12.3461-3464.2000

    authors: Durand R,Eslahpazire J,Jafari S,Delabre JF,Marmorat-Khuong A,di Piazza JP,Le Bras J

    更新日期:2000-12-01 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

  • Comparative antimalarial activities of six pairs of 1,2,4,5-tetraoxanes (peroxide dimers) and 1,2,4,5,7,8-hexaoxonanes (peroxide trimers).

    abstract::Six tetraoxanes had 50% inhibitory concentrations in the range of 10 to 100 ng/ml against Plasmodium falciparum, whereas the corresponding hexaoxonanes had minimal antimalarial activity. The lack of iron-mediated reactivity of the hexaoxonanes may explain their low activity compared to the tetraoxanes, the latter of w...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00264-07

    authors: Dong Y,Creek D,Chollet J,Matile H,Charman SA,Wittlin S,Wood JK,Vennerstrom JL

    更新日期:2007-08-01 00:00:00

  • Nitric Oxide-Mediated Induction of Dispersal in Pseudomonas aeruginosa Biofilms Is Inhibited by Flavohemoglobin Production and Is Enhanced by Imidazole.

    abstract::The biological signal molecule nitric oxide (NO) was found to induce biofilm dispersal across a range of bacterial species, which led to its consideration for therapeutic strategies to treat biofilms and biofilm-related infections. However, biofilms are often not completely dispersed after exposure to NO. To better un...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01832-17

    authors: Zhu X,Oh HS,Ng YCB,Tang PYP,Barraud N,Rice SA

    更新日期:2018-02-23 00:00:00

  • In vitro susceptibility of Coxiella burnetii to linezolid in comparison with its susceptibilities to quinolones, doxycycline, and clarithromycin.

    abstract::The in vitro susceptibility to linezolid shown by nine Greek isolates of Coxiella burnetii derived from patients with acute Q fever was investigated. MICs of linezolid were compared with those of pefloxacin, ciprofloxacin, ofloxacin, trovafloxacin, doxycycline, and clarithromycin using the shell vial assay. MICs of li...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.11.3276-3278.2001

    authors: Gikas A,Spyridaki I,Scoulica E,Psaroulaki A,Tselentis Y

    更新日期:2001-11-01 00:00:00

  • Intra- and Interlaboratory Agreement in Assessing the In Vitro Activity of Micafungin against Common and Rare Candida Species with the EUCAST, CLSI, and Etest Methods.

    abstract::The emergence of resistant strains among common and rare Candida species necessitates continuous monitoring of the in vitro susceptibilities of those isolates. We therefore assessed the in vitro activities of micafungin against 1,099 molecularly identified isolates belonging to 5 common and 20 rare Candida species by ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01027-16

    authors: Meletiadis J,Geertsen E,Curfs-Breuker I,Meis JF,Mouton JW

    更新日期:2016-09-23 00:00:00

  • Polyamine transport as a target for treatment of Pneumocystis pneumonia.

    abstract::Polyamine levels are greatly increased in alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP), leading to increased production of H(2)O(2), which causes AMs to undergo apoptosis. One of the mechanisms by which polyamine levels in AMs are elevated is enhanced uptake of exogenous polyamines. In this study, th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00662-09

    authors: Liao CP,Phanstiel O 4th,Lasbury ME,Zhang C,Shao S,Durant PJ,Cheng BH,Lee CH

    更新日期:2009-12-01 00:00:00

  • Olorofim Susceptibility Testing of 1,423 Danish Mold Isolates Obtained in 2018-2019 Confirms Uniform and Broad-Spectrum Activity.

    abstract::Olorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus Here, we explored the MIC variability in more detail and prospectively investigated the susceptibili...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01527-20

    authors: Astvad KMT,Jørgensen KM,Hare RK,Datcu R,Arendrup MC

    更新日期:2020-12-16 00:00:00

  • Synergistic activity between vancomycin or teicoplanin and gentamicin or tobramycin against pathogenic diphtheroids.

    abstract::The in vitro activities of vancomycin and teicoplanin alone and in combination with gentamicin or tobramycin were studied by time-kill techniques with 11 strains of pathogenic diphtheroids (Corynebacterium group JK). The activities of vancomycin and teicoplanin were similar (MIC for 90% of strains tested [MIC90], 1 mi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.32.4.434

    authors: Spitzer PG,Eliopoulos GM,Karchmer AW,Moellering RC Jr

    更新日期:1988-04-01 00:00:00

  • Synergistic activity of ceftriaxone combined with netilmicin administered once daily for treatment of experimental streptococcal endocarditis.

    abstract::We have conducted experiments to determine if one daily injection of netilmicin (NET) would be synergistic with the broad-spectrum cephalosporin ceftriaxone (CRO) in the treatment of experimentally induced endocarditis. Rats with catheter-induced aortic vegetations were infected intravenously with 3 x 10(7) CFU of a b...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.2.207

    authors: Francioli PB,Glauser MP

    更新日期:1993-02-01 00:00:00

  • Effects of Microplate Type and Broth Additives on Microdilution MIC Susceptibility Assays.

    abstract::The determination of antibiotic potency against bacterial strains by assessment of their minimum inhibitory concentration normally uses a standardized broth microdilution assay procedure developed more than 50 years ago. However, certain antibiotics require modified assay conditions in order to observe optimal activit...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01760-18

    authors: Kavanagh A,Ramu S,Gong Y,Cooper MA,Blaskovich MAT

    更新日期:2018-12-21 00:00:00

  • High in vitro activity of the novel spiropyrimidinetrione AZD0914, a DNA gyrase inhibitor, against multidrug-resistant Neisseria gonorrhoeae isolates suggests a new effective option for oral treatment of gonorrhea.

    abstract::We evaluated the activity of the novel spiropyrimidinetrione AZD0914 (DNA gyrase inhibitor) against clinical gonococcal isolates and international reference strains (n=250), including strains with diverse multidrug resistance and extensive drug resistance. The AZD0914 MICs were substantially lower than those of most o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.03090-14

    authors: Jacobsson S,Golparian D,Alm RA,Huband M,Mueller J,Jensen JS,Ohnishi M,Unemo M

    更新日期:2014-09-01 00:00:00

  • Modulation of gyrase-mediated DNA cleavage and cell killing by ATP.

    abstract::An uncoupler of oxidative phosphorylation, 2,4-dinitrophenol, and an aconitase inhibitor, fluoroacetic acid, both of which are known to lower the cellular ATP pool, protected Escherichia coli cells from the bactericidal actions of gyrase poisons including quinolone antibiotics, nalidixic acid and ciprofloxacin, and th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.42.5.1022

    authors: Li TK,Liu LF

    更新日期:1998-05-01 00:00:00

  • Effect of metronidazole resistance on bacterial eradication of Helicobacter pylori in infected children.

    abstract::A prospective study was performed with 23 Helicobacter pylori-infected children (mean age, 9.5 +/- 4.4 years) with clinical symptoms of gastritis and positive results of culture and histologic examination of gastric biopsy specimens to evaluate the influence of antibiotic resistance on eradication. Positive children w...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.42.6.1334

    authors: Raymond J,Kalach N,Bergeret M,Benhamou PH,Barbet JP,Gendrel D,Dupont C

    更新日期:1998-06-01 00:00:00

  • Acidometric agar plate method for ampicillin susceptibility testing of Haemophilus influenzae.

    abstract::The need for an accurate and rapid method of testing ampicillin susceptibility of Haemophilus influenzae, especially strains isolated from patients with meningitis and septicemia, is indisputable. Various methods have been employed for this purpose. Each has advantages and disadvantages. This report describes a modifi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.13.2.318

    authors: Park CH,Lopez JS,Cook CB

    更新日期:1978-02-01 00:00:00

  • Cilastatin does not alter superoxide dismutase activity.

    abstract::Cilastatin inhibits dehydropeptidase-I, a zinc metaloenzyme that metabolizes imipenem. Because zinc stabilizes the mammalian superoxide dismutase, we postulated that cilastatin would also inhibit the dismutase. Cilastatin concentrations at levels threefold higher than those expected in urine, however, did not inhibit ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.28.5.691

    authors: Proctor RA,Textor JA

    更新日期:1985-11-01 00:00:00