Inhibitors of sterol biosynthesis and amphotericin B reduce the viability of pneumocystis carinii f. sp. carinii.

Abstract:

:Pneumocystis carinii synthesizes sterols with a double bond at C-7 of the sterol nucleus and an alkyl group with one or two carbons at C-24 of the side chain. Also, some human-derived Pneumocystis carinii f. sp. hominis strains contain lanosterol derivatives with an alkyl group at C-24. These unique sterols have not been found in other pathogens of mammalian lungs. Thus, P. carinii may have important differences in its susceptibility to drugs known to block reactions in ergosterol biosynthesis in other fungi. In the present study, inhibitors of 3-hydroxy-3-methyglutaryl coenzyme A reductase, squalene synthase, squalene epoxidase, squalene epoxide-lanosterol cyclase, lanosterol demethylase, Delta(8) to Delta(7) isomerase, and S-adenosylmethionine:sterol methyltransferase were tested for their effects on P. carinii viability as determined by quantitation of cellular ATP levels in a population of organisms. Compounds within each category varied in inhibitory effect; the most effective included drugs targeted at squalene synthase, squalene epoxide-lanosterol cyclase, and Delta(8) to Delta(7) isomerase. Some drugs that are potent against ergosterol-synthesizing fungi had little effect against P. carinii, suggesting that substrates and/or enzymes in P. carinii sterol biosynthetic reactions are distinct. Amphotericin B is ineffective in clearing P. carinii infections at clinical doses; however, this drug apparently binds to sterols and causes permeability changes in P. carinii membranes, since it reduced cellular ATP levels in a dose-dependent fashion.

authors

Kaneshiro ES,Collins MS,Cushion MT

doi

10.1128/aac.44.6.1630-1638.2000

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

1630-8

issue

6

eissn

0066-4804

issn

1098-6596

journal_volume

44

pub_type

杂志文章
  • Sequences of wild-type and mutant ampD genes of Citrobacter freundii and Enterobacter cloacae.

    abstract::The ampD gene product regulates the expression of AmpC beta-lactamase in gram-negative bacteria and is proposed to be involved in peptidoglycan metabolism. In this study, we sequenced the ampD wild type and three mutant genes of Enterobacter cloacae and Citrobacter freundii. They exhibited a high degree of homology wi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.37.2.224

    authors: Kopp U,Wiedemann B,Lindquist S,Normark S

    更新日期:1993-02-01 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

    doi:10.1128/aac.44.11.3040-3048.2000

    authors: Wang ZX,Li SM,Heide L

    更新日期:2000-11-01 00:00:00

  • Comparison of the inoculum effect of cefoxitin and other cephalosporins and of beta-lactamase inhibitors and their penicillin-derived components on the Bacteroides fragilis group.

    abstract::We compared the inoculum effects for 109 recent clinical isolates of the Bacteroides fragilis group of cefoxitin, cefotetan, ceftizoxime, ceftriaxone, and three beta-lactamase inhibitors (clavulanic acid, sulbactam, and tazobactam) and their penicillin-derived components. Bactericidal activity was assayed and morpholo...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.35.9.1868

    authors: Goldstein EJ,Citron DM,Cherubin CE

    更新日期:1991-09-01 00:00:00

  • In vitro selection and in vivo efficacy of piperazine- and alkanediamide-linked bisbenzamidines against Pneumocystis pneumonia in mice.

    abstract::Bisbenzamidines, such as pentamidine isethionate, are aromatic dicationic compounds that are active against Pneumocystis and other microbes but are oftentimes toxic to the host. To identify potential anti-Pneumocystis agents, we synthesized bisbenzamidine derivatives in which the parent compound pentamidine was modifi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00126-06

    authors: Cushion MT,Walzer PD,Ashbaugh A,Rebholz S,Brubaker R,Vanden Eynde JJ,Mayence A,Huang TL

    更新日期:2006-07-01 00:00:00

  • Comparison of Cytomegalovirus Terminase Gene Mutations Selected after Exposure to Three Distinct Inhibitor Compounds.

    abstract::Letermovir, GW275175X (a benzimidazole), and tomeglovir (Bay38-4766) are chemically unrelated human cytomegalovirus (CMV) terminase complex inhibitors that have been tested in human subjects. UL56 gene mutations are the dominant pathway of letermovir resistance, while UL89 and UL56 mutations are known to confer benzim...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01325-17

    authors: Chou S

    更新日期:2017-10-24 00:00:00

  • Rapid microbiological assay for chlorhydroxyquinoline that uses a cryogenically stored inoculum.

    abstract::A rapid microbiological assay for chlorhydroxyquinoline is described. It is a turbidimetric procedure that uses Streptococcus faecalis as the test organism. Results are available within 5 h. Data are presented to show the advantages of using a cryogenically stored inoculum over an inoculum prepared on a daily basis. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.11.5.848

    authors: Cosgrove RF

    更新日期:1977-05-01 00:00:00

  • Cinoxacin: effectiveness against experimental pyelonephritis in rats.

    abstract::The antimicrobial activity of cinoxacin, 1-ethyl-4(1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, previously reported as compound 64716, was determined and compared with other antimicrobial agents at a dosage of 12 mg/kg once daily in a descending pyelonephritis rat model with Escherichia coli and Proteus mir...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.6.4.432

    authors: Holmes DH,Ensminger PW,Gordee RS

    更新日期:1974-10-01 00:00:00

  • High-level tetracycline resistance in Neisseria gonorrhoeae is result of acquisition of streptococcal tetM determinant.

    abstract::Recently, strains of Neisseria gonorrhoeae have been isolated which are highly resistant to tetracycline (MICs of 16 to 64 micrograms/ml). This resistance was due to the acquisition of the resistance determinant tetM, a transposon-borne determinant initially found in the genus Streptococcus and more recently in Mycopl...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.30.5.664

    authors: Morse SA,Johnson SR,Biddle JW,Roberts MC

    更新日期:1986-11-01 00:00:00

  • Comparative DNA analysis of two vanA plasmids from Enterococcus faecium strains isolated from poultry and a poultry farmer in Norway.

    abstract::The DNA sequences of two plasmids carrying vanA, pVEF1 (39,626 bp) and pVEF2 (39,714 bp), were determined. Forty-three shared coding sequences were identified, and the only nucleotide difference was an 88-bp indel. A postsegregational killing system was identified. This system possibly explains the persistence of the ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00557-06

    authors: Sletvold H,Johnsen PJ,Simonsen GS,Aasnaes B,Sundsfjord A,Nielsen KM

    更新日期:2007-02-01 00:00:00

  • Successful Systemic and Topical Treatment of Mycobacterium abscessus Otomastoiditis.

    abstract::Mycobacterium abscessus is an extensively drug-resistant opportunistic pathogen that can cause chronic otomastoiditis. There are no evidence-based treatment regimens for this severe infection. We treated four children with M. abscessus otomastoiditis with a structured regimen of topical imipenem and tigecycline, intra...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01203-19

    authors: van Wijk F,Waterval J,van Aerde K,Henriet SSV,Meijer FJA,Borra LC,Aarnoutse RE,van Ingen J

    更新日期:2019-12-20 00:00:00

  • Identification of TEM-135 beta-lactamase in penicillinase-producing Neisseria gonorrhoeae strains in Japan.

    abstract::Ten penicillinase-producing Neisseria gonorrhoeae (PPNG) strains isolated from 2000 to 2008 were characterized by multilocus sequence typing, multiantigen sequence typing, and plasmid typing. Sequence analysis showed that 8 strains contained a TEM-1 beta-lactamase gene. However, two other genetically distinct PPNG str...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00245-10

    authors: Ohnishi M,Ono E,Shimuta K,Watanabe H,Okamura N

    更新日期:2010-07-01 00:00:00

  • Treatment of invasive fungal infections in renally impaired patients with amphotericin B colloidal dispersion.

    abstract::Amphotericin B colloidal dispersion (ABCD) is a new formulation of conventional amphotericin B designed to minimize drug distribution in the kidney and reduce nephrotoxicity. We studied the safety and efficacy of ABCD in 133 renally compromised patients with invasive fungal infections. Patients had either nephrotoxici...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1128/AAC.42.3.606

    authors: Anaissie EJ,Mattiuzzi GN,Miller CB,Noskin GA,Gurwith MJ,Mamelok RD,Pietrelli LA

    更新日期:1998-03-01 00:00:00

  • Bioavailability of oral trimetrexate in patients with acquired immunodeficiency syndrome.

    abstract::The combination of the lipophilic antifolate trimetrexate and the rescue agent leucovorin has shown promise in the treatment of Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome. The pharmacokinetic behavior of trimetrexate administered either by intravenous bolus or orally was studied...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.32.3.324

    authors: Rogers P,Allegra CJ,Murphy RF,Drake JC,Masur H,Poplack DG,Chabner BA,Parrillo JE,Lane HC,Balis FM

    更新日期:1988-03-01 00:00:00

  • High-level cefixime- and ceftriaxone-resistant Neisseria gonorrhoeae in France: novel penA mosaic allele in a successful international clone causes treatment failure.

    abstract::Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefix...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.05760-11

    authors: Unemo M,Golparian D,Nicholas R,Ohnishi M,Gallay A,Sednaoui P

    更新日期:2012-03-01 00:00:00

  • Effect of virginiamycin on the growth cycle of Bdellovibrio.

    abstract::The two components of virginiamycin, virginiamycin M (VM) and virginiamycin S (VS), were used to explore the life cycle of symbiosis-dependent and -independent strains of Bdellovibrio bacteriovorus during multiplication in a two-membered system with either living or heat-inactivated Escherichia coli or in axenic cultu...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.9.1.179

    authors: Varon M,Cocito C,Seijffers J

    更新日期:1976-01-01 00:00:00

  • Accumulation of norfloxacin by Bacteroides fragilis.

    abstract::The accumulation of norfloxacin by Bacteroides fragilis NCTC 9343 was determined by the modified fluorescence method. The time required to achieve a steady-state concentration (SSC) after allowing B. fragilis to accumulate norfloxacin in an aerobic or an anaerobic environment was approximately 2 min; the SSC achieved ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.9.2361-2366.2000

    authors: Ricci V,Piddock LJ

    更新日期:2000-09-01 00:00:00

  • Evaluation of a mouse model of necrotic granuloma formation using C3HeB/FeJ mice for testing of drugs against Mycobacterium tuberculosis.

    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

    authors: Driver ER,Ryan GJ,Hoff DR,Irwin SM,Basaraba RJ,Kramnik I,Lenaerts AJ

    更新日期:2012-06-01 00:00:00

  • Emergence of a novel lamivudine-resistant hepatitis B virus variant with a substitution outside the YMDD motif.

    abstract::Lamivudine is a major drug approved for treatment of chronic hepatitis B virus (HBV) infection. Emergence of drug-resistant mutants with amino acid substitutions in the YMDD motif is a well-documented problem during long-term lamivudine therapy. Here we report a novel lamivudine-resistant strain of HBV with an intact ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00239-06

    authors: Yatsuji H,Noguchi C,Hiraga N,Mori N,Tsuge M,Imamura M,Takahashi S,Iwao E,Fujimoto Y,Ochi H,Abe H,Maekawa T,Tateno C,Yoshizato K,Suzuki F,Kumada H,Chayama K

    更新日期:2006-11-01 00:00:00

  • Comparison of 5-episisomicin (Sch 22591), gentamicin, sisomicin, and tobramycin in treatment of experimental Pseudomonas infections in mice.

    abstract::Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12 Pseudomonas strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.14.6.824

    authors: Goering RV,Sanders CC,Sanders WE Jr

    更新日期:1978-12-01 00:00:00

  • Entecavir for treatment of hepatitis B virus displays no in vitro mitochondrial toxicity or DNA polymerase gamma inhibition.

    abstract::Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Entecavir (ETV) is an approved deoxyguanosine nucleoside for the treatment of...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01122-07

    authors: Mazzucco CE,Hamatake RK,Colonno RJ,Tenney DJ

    更新日期:2008-02-01 00:00:00

  • Foscarnet for suppression of human immunodeficiency virus replication.

    abstract::The effect of foscarnet against human immunodeficiency virus (HIV) was evaluated in nine HIV-infected individuals; six completed 28 days of induction therapy. The overall mean increase in CD4+ lymphocytes was 64 cells per mm3. The mean decline in the HIV antigen concentration was 108 pg/ml (P = 0.03), and suppression ...

    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.38.3.604

    authors: Fletcher CV,Collier AC,Rhame FS,Bennett D,Para MF,Beatty CC,Jones CE,Balfour HH Jr

    更新日期:1994-03-01 00:00:00

  • Fluconazole Susceptibility in Cryptococcus gattii Is Dependent on the ABC Transporter Pdr11.

    abstract::Cryptococcus gattii isolates from the Pacific Northwest have exhibited higher fluconazole MICs than isolates from other sites. The mechanism of fluconazole resistance in C. gattii is unknown. We sought to determine the role of the efflux pumps Mdr1 and Pdr11 in fluconazole susceptibility. Using biolistic transformatio...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01777-15

    authors: Yang ML,Uhrig J,Vu K,Singapuri A,Dennis M,Gelli A,Thompson GR 3rd

    更新日期:2015-12-07 00:00:00

  • In vitro inhibition of Streptococcus mutans biofilm formation on hydroxyapatite by subinhibitory concentrations of anthraquinones.

    abstract::We report that certain anthraquinones (AQs) reduce Streptococcus mutans biofilm formation on hydroxyapatite at concentrations below the MIC. Although AQs are known to generate reactive oxygen species, the latter do not underlie the observed effect. Our results suggest that AQs inhibit S. mutans biofilm formation by ca...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00999-06

    authors: Coenye T,Honraet K,Rigole P,Nadal Jimenez P,Nelis HJ

    更新日期:2007-04-01 00:00:00

  • Potent in vitro antimalarial activity of metacycloprodigiosin isolated from Streptomyces spectabilis BCC 4785.

    abstract::Bioassay-guided fractionation of the extract from the fermentation broth of Streptomyces spectabilis BCC 4785 led to the isolation of three principle antimalarial agents, metacycloprodigiosin, bafilomycin A(1), and spectinabilin. Metacycloprodigiosin exhibited potent in vitro activity against Plasmodium falciparum K1,...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.4.1112-1113.2002

    authors: Isaka M,Jaturapat A,Kramyu J,Tanticharoen M,Thebtaranonth Y

    更新日期:2002-04-01 00:00:00

  • Evidence for transfer of CMY-2 AmpC beta-lactamase plasmids between Escherichia coli and Salmonella isolates from food animals and humans.

    abstract::Escherichia coli is an important pathogen that shows increasing antimicrobial resistance in isolates from both animals and humans. Our laboratory recently described Salmonella isolates from food animals and humans that expressed an identical plasmid-mediated, AmpC-like beta-lactamase, CMY-2. In the present study, 59 o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.10.2716-2722.2001

    authors: Winokur PL,Vonstein DL,Hoffman LJ,Uhlenhopp EK,Doern GV

    更新日期:2001-10-01 00:00:00

  • Discovery and analysis of 4H-pyridopyrimidines, a class of selective bacterial protein synthesis inhibitors.

    abstract::Bacterial protein synthesis is the target for numerous natural and synthetic antibacterial agents. We have developed a poly(U) mRNA-directed aminoacylation/translation protein synthesis system composed of phenyl-tRNA synthetases, ribosomes, and ribosomal factors from Escherichia coli. This system, utilizing purified c...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00638-10

    authors: Ribble W,Hill WE,Ochsner UA,Jarvis TC,Guiles JW,Janjic N,Bullard JM

    更新日期:2010-11-01 00:00:00

  • Comparison of in vitro antimicrobial susceptibilities of Mycobacterium avium-M. intracellulare strains from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and animal sources.

    abstract::Difloxacin, A-56620, cefazolin, cefotaxime, ceftizoxime, cephapirin, SK&F 88070, and spectinomycin were used to compare the in vitro susceptibilities of Mycobacterium avium-M. intracellular isolates from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and diseased animals. Against the i...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.7.1390

    authors: Byrne SK,Geddes GL,Isaac-Renton JL,Black WA

    更新日期:1990-07-01 00:00:00

  • Mycobacterium tuberculosis embB codon 306 mutations confer moderately increased resistance to ethambutol in vitro and in vivo.

    abstract::Ethambutol (EMB) is a major component of the first-line therapy of tuberculosis. Mutations in codon 306 of embB (embB306) were suggested as a major resistance mechanism in clinical isolates. To directly analyze the impact of individual embB306 mutations on EMB resistance, we used allelic exchange experiments to genera...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00007-10

    authors: Plinke C,Walter K,Aly S,Ehlers S,Niemann S

    更新日期:2011-06-01 00:00:00

  • Frequency of voriconazole resistance in vitro among Spanish clinical isolates of Candida spp. According to breakpoints established by the Antifungal Subcommittee of the European Committee on Antimicrobial Susceptibility Testing.

    abstract::A total of 4,226 Spanish clinical isolates of Candida spp. were analyzed to assess resistance to voriconazole according to breakpoints established by the European Committee for Antimicrobial Susceptibility Testing (where susceptibility [S] to voriconazole corresponds to a MIC of ≤ 0.12 mg/liter). Resistance was uncomm...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01757-10

    authors: Cuenca-Estrella M,Gomez-Lopez A,Cuesta I,Zaragoza O,Mellado E,Rodriguez-Tudela JL,Antifungal Subcommittee of European Committee on Antimicrobial Susceptibility Testing.

    更新日期:2011-04-01 00:00:00

  • Absorption and excretion of miloxacin in mice, rats, and dogs.

    abstract::Miloxacin, a synthetic antibacterial agent structurally related to oxolinic acid, has a broad spectrum of activity in vitro against gram-negative bacteria and considerable activity in vivo against infections with these bacteria. These observations led to studies on the absorption and excretion of miloxacin in mice, ra...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.18.1.41

    authors: Izawa A,Yoshitake A,Komatsu T

    更新日期:1980-07-01 00:00:00