Azole susceptibility and hyphal formation in a cytochrome P-450-deficient mutant of Candida albicans.

Abstract:

:A cytochrome P-450-deficient mutant of Candida albicans, strain D10, was employed to study the mode of action of imidazole antifungal agents. This mutant accumulates exclusively 14-alpha-methylsterols, resulting in a sterol profile which mimics that of azole-treated wild-type strains. Since the widely accepted primary effect of imidazoles is the inhibition of cytochrome P-450-mediated demethylation of the ergosterol precursor lanosterol, strain D10 and its wild-type revertant, strain D10R, were grown in the presence of concentrations of clotrimazole, miconazole, and ketoconazole known to inhibit demethylation. The growth of strain D10 was unaffected by these antifungal agents, while that of strain D10R was significantly reduced. At higher azole concentrations (which are known to exert a direct, disruptive action on the cell membrane), the growth of both strains was immediately and completely inhibited by clotrimazole and miconazole. Ketoconazole was membrane disruptive only for strain D10; this is the first report of a direct membrane effect for this drug. Because hyphal formation has been implicated in the pathogenesis of C. albicans and because it has been shown to be inhibited by azoles, the hypha-forming capability of strain D10 was examined. Strain D10 was shown to be seriously defective in hyphal formation, suggesting that this function may be dependent on the 14-alpha-demethylation of lanosterol. The results of this study suggest that inhibition of lanosterol demethylation per se is neither fungicidal nor fungistatic, although the growth rate is reduced. In addition, the substitution of 14-alpha-methylsterols for ergosterol results in defective hyphal formation and in a cell that is more susceptible to membrane-active agents such as ketoconazole.

authors

Lees ND,Broughton MC,Sanglard D,Bard M

doi

10.1128/aac.34.5.831

subject

Has Abstract

pub_date

1990-05-01 00:00:00

pages

831-6

issue

5

eissn

0066-4804

issn

1098-6596

journal_volume

34

pub_type

杂志文章
  • Efficacy of acyclovir against mouse cytomegalovirus in vivo.

    abstract::Acyclovir reduced mortality and organ virus titers in mice inoculated intraperitoneally with 10 50% lethal doses of mouse cytomegalovirus. This susceptibility to acyclovir of a herpesvirus which lacks thymidine kinase is surprising. Alternative phosphorylating enzymes may account for this susceptibility. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.20.2.275

    authors: Wingard JR,Bender WJ,Saral R,Burns WH

    更新日期:1981-08-01 00:00:00

  • Mycobacterium smegmatis D-Alanine Racemase Mutants Are Not Dependent on D-Alanine for Growth.

    abstract::Mycobacterium smegmatis is a fast-growing nonpathogenic species particularly useful in studying basic cellular processes of relevance to pathogenic mycobacteria. This study focused on the D-alanine racemase gene (alrA), which is involved in the synthesis of D-alanine, a basic component of peptidoglycan that forms the ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.2.47-54.2002

    authors: Chacon O,Feng Z,Harris NB,Cáceres NE,Adams LG,Barletta RG

    更新日期:2002-01-01 00:00:00

  • Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome.

    abstract::Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were sele...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.32.9.1392

    authors: Yajko DM,Kirihara J,Sanders C,Nassos P,Hadley WK

    更新日期:1988-09-01 00:00:00

  • Aspergillus fumigatus forms biofilms with reduced antifungal drug susceptibility on bronchial epithelial cells.

    abstract::Aspergillus fumigatus is a leading cause of death in immunocompromised patients and a frequent colonizer of the respiratory tracts of asthma and cystic fibrosis (CF) patients. Biofilms enable bacteria and yeasts to persist in infections and can contribute to antimicrobial resistance. We investigated the ability of A. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00234-08

    authors: Seidler MJ,Salvenmoser S,Müller FM

    更新日期:2008-11-01 00:00:00

  • Antimyocarditic activity of the guanine derivative BIOLF-70 in a coxsackievirus B3 murine model.

    abstract::Prophylactic administration of a nontoxic dose of 9-[[2-benzyloxyl-1-(benzyloxymethyl)ethoxy]methyl]-6-chlo roguanine (BIOLF-70) to mice reduced the number of myocarditic lesions induced by coxsackievirus B3 (CVB3). BIOLF-70 exhibited minimal antiviral activity against CVB3 in HeLa cells and murine neonatal skin fibro...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.27.2.184

    authors: Gauntt CJ,Arizpe HM,Kung JT,Ogilvie KK,Cheriyan UO

    更新日期:1985-02-01 00:00:00

  • In vitro inhibition of bacterial DNA gyrase by cinodine, a glycocinnamoylspermidine antibiotic.

    abstract::Cinodine, a broad-spectrum glycocinnamoylspermidine antibiotic, binds to DNA and irreversibly inhibits bacterial and phase DNA synthesis. Cinodine was found to inhibit the activity of Micrococcus luteus DNA gyrase in vitro, but it did not inhibit the activities of two other DNA-binding enzymes, namely, topoisomerase I...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.7.1450

    authors: Osburne MS,Maiese WM,Greenstein M

    更新日期:1990-07-01 00:00:00

  • Lysostaphin-coated catheters eradicate Staphylococccus aureus challenge and block surface colonization.

    abstract::Lysostaphin is an endopeptidase that kills Staphylococcus aureus, a predominant organism in catheter-related infections. Lysostaphin-coated catheters prevented catheter colonization by several strains of S. aureus, and activity was maintained for at least 4 days. Prophylactic use of lysostaphin in catheters may help p...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.48.7.2704-2707.2004

    authors: Shah A,Mond J,Walsh S

    更新日期:2004-07-01 00:00:00

  • Involvement of multidrug resistance-associated protein 2 in intestinal secretion of grepafloxacin in rats.

    abstract::We investigated the contribution of multidrug resistance-associated protein 2 (MRP2) to the secretory transport of grepafloxacin and compared its functional role with that of P-glycoprotein (P-gp) by using Sprague-Dawley rats (SDRs) and Eisai hyperbilirubinemic rats (EHBRs), in which MRP2 is hereditarily defective. In...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.46.2.344-349.2002

    authors: Naruhashi K,Tamai I,Inoue N,Muraoka H,Sai Y,Suzuki N,Tsuji A

    更新日期:2002-02-01 00:00:00

  • Repeated Detection of Carbapenemase-Producing Escherichia coli in Gulls Inhabiting Alaska.

    abstract::Here, we report the first detection of carbapenemase-producing Escherichia coli in Alaska and in wildlife in the United States. Wild bird (gull) feces sampled at three locations in Southcentral Alaska yielded isolates that harbored plasmid-encoded blaKPC-2 or chromosomally encoded blaOXA-48 and genes associated with a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00758-19

    authors: Ahlstrom CA,Ramey AM,Woksepp H,Bonnedahl J

    更新日期:2019-07-25 00:00:00

  • Antibiofilm effects of azithromycin and erythromycin on Porphyromonas gingivalis.

    abstract::Antibiotic resistance of biofilm-grown bacteria contributes to chronic infections, such as marginal and periapical periodontitis, which are strongly associated with Porphyromonas gingivalis. Concurrent azithromycin (AZM) administration and mechanical debridement improve the clinical parameters of periodontal tissue in...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.05169-11

    authors: Maezono H,Noiri Y,Asahi Y,Yamaguchi M,Yamamoto R,Izutani N,Azakami H,Ebisu S

    更新日期:2011-12-01 00:00:00

  • Role of Interleukin-12 in Protection against Pulmonary Infection with Methicillin-Resistant Staphylococcus aureus.

    abstract::Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen associated with nosocomial pneumonia and is an increasing threat for severe community-acquired pneumonia. We have now investigated the role of interleukin-12 (IL-12) in protective immunity against lung infection with MRSA. The importance of IL-12 ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00968-15

    authors: Nguyen QT,Furuya Y,Roberts S,Metzger DW

    更新日期:2015-10-01 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

  • Lack of an effect of antibiotic treatment on prolonged detection of chlamydial DNA in murine genital tract infection.

    abstract::Mice treated with antibiotics early or late after active infection had resolved were examined for chlamydial DNA in endocervical swabs. The early eradication of infection limited oviduct pathology, despite the continued detection of chlamydial DNA by nested PCR. Late antibiotic treatment had no effect on the ability t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00231-07

    authors: Reeves DM,Nagarajan U,O'Connell C,Andrews CW Jr,Darville T

    更新日期:2007-07-01 00:00:00

  • Ramoplanin at bactericidal concentrations induces bacterial membrane depolarization in Staphylococcus aureus.

    abstract::Ramoplanin is an actinomycetes-derived antibiotic with broad-spectrum activity against Gram-positive bacteria that has been evaluated in clinical trials for the treatment of gastrointestinal vancomycin-resistant enterococci (VRE) and Clostridium difficile infections. Recent studies have proposed that ramoplanin binds ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00061-14

    authors: Cheng M,Huang JX,Ramu S,Butler MS,Cooper MA

    更新日期:2014-11-01 00:00:00

  • Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma.

    abstract::The disposition of caspofungin, a parenteral antifungal drug, was investigated. Following a single, 1-h, intravenous infusion of 70 mg (200 microCi) of [(3)H]caspofungin to healthy men, plasma, urine, and feces were collected over 27 days in study A (n = 6) and plasma was collected over 26 weeks in study B (n = 7). Su...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 临床试验,杂志文章

    doi:10.1128/aac.48.3.815-823.2004

    authors: Stone JA,Xu X,Winchell GA,Deutsch PJ,Pearson PG,Migoya EM,Mistry GC,Xi L,Miller A,Sandhu P,Singh R,deLuna F,Dilzer SC,Lasseter KC

    更新日期:2004-03-01 00:00:00

  • Orally Efficacious Broad-Spectrum Ribonucleoside Analog Inhibitor of Influenza and Respiratory Syncytial Viruses.

    abstract::Morbidity and mortality resulting from influenza-like disease are a threat, especially for older adults. To improve case management, next-generation broad-spectrum antiviral therapeutics that are efficacious against major drivers of influenza-like disease, including influenza viruses and respiratory syncytial virus (R...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00766-18

    authors: Yoon JJ,Toots M,Lee S,Lee ME,Ludeke B,Luczo JM,Ganti K,Cox RM,Sticher ZM,Edpuganti V,Mitchell DG,Lockwood MA,Kolykhalov AA,Greninger AL,Moore ML,Painter GR,Lowen AC,Tompkins SM,Fearns R,Natchus MG,Plemper RK

    更新日期:2018-07-27 00:00:00

  • Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease.

    abstract::Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD cause...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00011-18

    authors: Jhun BW,Yang B,Moon SM,Lee H,Park HY,Jeon K,Kwon OJ,Ahn J,Moon IJ,Shin SJ,Daley CL,Koh WJ

    更新日期:2018-06-26 00:00:00

  • Kappacin, a novel antibacterial peptide from bovine milk.

    abstract::Caseinomacropeptide (CMP) is a heterogeneous C-terminal fragment (residues 106 to 169) of bovine milk kappa-casein composed of glycosylated and phosphorylated forms of different genetic variants. We have demonstrated that CMP has growth-inhibitory activity against the oral opportunistic pathogens Streptococcus mutans ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.8.2309-2315.2001

    authors: Malkoski M,Dashper SG,O'Brien-Simpson NM,Talbo GH,Macris M,Cross KJ,Reynolds EC

    更新日期:2001-08-01 00:00:00

  • Inducible resistance of fish bacterial pathogens to the antimicrobial peptide cecropin B.

    abstract::Cecropin B is a cationic antimicrobial peptide originally isolated from the diapausing pupae of the giant silk moth, Hylphora cecropia. Cecropin B elicits its antimicrobial effects through disruption of the anionic cell membranes of gram-negative bacteria. Previous work by our laboratory demonstrated that a constituti...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00023-08

    authors: Sallum UW,Chen TT

    更新日期:2008-09-01 00:00:00

  • Biosynthetic studies on antibiotic A47934.

    abstract::A47934, a peptide antibiotic produced by Streptomyces toyocaensis, belongs to the glycopeptide class of compounds which includes ristocetin and vancomycin. Incorporation studies with radioisotope-labeled substrates indicated that tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylate, acetate, and sulfate were ef...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.31.10.1497

    authors: Zmijewski MJ Jr,Briggs B,Logan R,Boeck LD

    更新日期:1987-10-01 00:00:00

  • Autoradiographic localization of [3H]gentamicin in the proximal renal tubules of mice.

    abstract::The site of localization of [(3)H]gentamicin within mouse kidney is shown to be the proximal renal tubule by coincidence of the radioactivity, as visualized by autoradiography, and the mucopolysaccharide-rich microvilli characteristic of proximal convoluted tubules, as visualized by histochemical staining. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.15.1.131

    authors: Kuhar MJ,Mak LL,Lietman PS

    更新日期:1979-01-01 00:00:00

  • Emergence of cfr-Mediated Linezolid Resistance in a Methicillin-Resistant Staphylococcus aureus Epidemic Clone Isolated from Patients with Cystic Fibrosis.

    abstract::Resistance to linezolid (LZD) in methicillin-resistant Staphylococcus aureus (MRSA) isolates from patients with cystic fibrosis (CF) is due mainly to ribosomal mutations. We report on four CF patients with LZD-resistant MRSA bronchopulmonary infections by strains carrying the cfr gene. Strains from one patient also ha...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02067-15

    authors: de Dios Caballero J,Pastor MD,Vindel A,Máiz L,Yagüe G,Salvador C,Cobo M,Morosini MI,del Campo R,Cantón R,GEIFQ Study Group.

    更新日期:2015-12-14 00:00:00

  • Effects of atovaquone and other inhibitors on Pneumocystis carinii dihydroorotate dehydrogenase.

    abstract::Dihydroorotate dehydrogenase (DHOD) is a pyrimidine biosynthetic enzyme which is usually directly linked to the mitochondrial respiratory chain. Antimalarial naphthoquinones such as atovaquone (566c80) inhibit malarial DHOD by inhibiting electron transport. Since atovaquone also has therapeutic activity against Pneumo...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.39.2.325

    authors: Ittarat I,Asawamahasakda W,Bartlett MS,Smith JW,Meshnick SR

    更新日期:1995-02-01 00:00:00

  • In vitro susceptibility of Capnocytophaga species to 29 antimicrobial agents.

    abstract::A hemoglobin-supplemented medium composed of Columbia agar base supplemented with 1% hemoglobin and 1% Polyvitex was used to investigate the in vitro activity of 29 antimicrobial agents against Capnocytophaga species. Clindamycin was the most active agent, with all strains being inhibited by 0.06 microgram/ml or less....

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.30.5.739

    authors: Rummens JL,Gordts B,Van Landuyt HW

    更新日期:1986-11-01 00:00:00

  • Virulence factors and TEM-type β-lactamases produced by two isolates of an epidemic Klebsiella pneumoniae strain.

    abstract::Two Klebsiella pneumoniae isolates of the same strain, identified in Poland, produced either TEM-47 or TEM-68, which differed by the Arg275Leu substitution. They harbored a few virulence factors, including an iron-chelating factor and capsule overproduction, suggesting that these factors were sufficient to enhance the...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.05079-11

    authors: Robin F,Hennequin C,Gniadkowski M,Beyrouthy R,Empel J,Gibold L,Bonnet R

    更新日期:2012-02-01 00:00:00

  • Rifampin and rifabutin resistance mechanism in Helicobacter pylori.

    abstract::Eighty-one clinical isolates of Helicobacter pylori showed no resistance to rifampin (MIC range, 0.032 to 2 microg/ml; MIC at which 50% of isolates are inhibited [MIC50], 0.25 microg/ml). The MIC50 of rifabutin was 0.008 microg/ml (n = 16). All resistant laboratory mutants of H. pylori ATCC 43504 showed amino acid exc...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.43.6.1497

    authors: Heep M,Beck D,Bayerdörffer E,Lehn N

    更新日期:1999-06-01 00:00:00

  • Antimicrobial activity of betaine esters, quaternary ammonium amphiphiles which spontaneously hydrolyze into nontoxic components.

    abstract::A series of quaternary ammonium compounds that are esters of betaine and fatty alcohols with hydrocarbon chain lengths of 10 to 18 carbon atoms were tested with respect to antimicrobial activities and rates of hydrolysis. When the tetradecyl derivative was tested against some selected microorganisms, the killing effec...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.34.10.1949

    authors: Lindstedt M,Allenmark S,Thompson RA,Edebo L

    更新日期:1990-10-01 00:00:00

  • Metformin Suppresses Development of the Echinococcus multilocularis Larval Stage by Targeting the TOR Pathway.

    abstract::Alveolar echinococcosis (AE) is a severe disease caused by the larval stage of the tapeworm Echinococcus multilocularis Current chemotherapeutic treatment options based on benzimidazoles are of limited effectiveness, which underlines the need to find new antiechinococcosis drugs. Metformin is an antihyperglycemic and ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01808-19

    authors: Loos JA,Dávila VA,Brehm K,Cumino AC

    更新日期:2020-08-20 00:00:00

  • Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

    abstract::There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01289-15

    authors: Djoko KY,Goytia MM,Donnelly PS,Schembri MA,Shafer WM,McEwan AG

    更新日期:2015-10-01 00:00:00

  • In vitro and in vivo antibacterial activities of K-4619, a new semisynthetic aminoglycoside.

    abstract::The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia specie...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.26.2.187

    authors: Saino Y,Hattori Y,Koshi T,Kobayashi F,Oda T,Mitsuhashi S

    更新日期:1984-08-01 00:00:00