Abstract:
:Ergosterol, a fungus-specific sterol enriched in cell plasma membranes, is an effective antifungal drug target. However, current knowledge of the ergosterol biosynthesis process in the saprophytic human fungal pathogen Aspergillus fumigatus remains limited. In this study, we found that two endoplasmic reticulum-localized sterol C-24 reductases encoded by both erg4A and erg4B homologs are required to catalyze the reaction during the final step of ergosterol biosynthesis. Loss of one homolog of Erg4 induces the overexpression of the other one, accompanied by almost normal ergosterol synthesis and wild-type colony growth. However, double deletions of erg4A and erg4B completely block the last step of ergosterol synthesis, resulting in the accumulation of ergosta-5,7,22,24(28)-tetraenol, a precursor compound of ergosterol. Further studies indicate that erg4A and erg4B are required for conidiation but not for hyphal growth. Importantly, the Δerg4A Δerg4B mutant still demonstrates wild-type virulence in a compromised mouse model but displays remarkable increased susceptibility to antifungal azoles. Our data suggest that inhibitors of Erg4A and Erg4B may serve as effective candidates for adjunct antifungal agents with azoles. IMPORTANCE:Knowledge of the ergosterol biosynthesis pathway in the human opportunistic pathogen A. fumigatus is useful for designing and finding new antifungal drugs. In this study, we demonstrated that the endoplasmic reticulum-localized sterol C-24 reductases Erg4A and Erg4B are required for conidiation via regulation of ergosterol biosynthesis. Moreover, inactivation of both Erg4A and Erg4B results in hypersensitivity to the clinical guideline-recommended antifungal drugs itraconazole and voriconazole. Therefore, our finding indicates that inhibition of Erg4A and Erg4B might be an effective approach for alleviating A. fumigatus infection.
journal_name
Appl Environ Microbioljournal_title
Applied and environmental microbiologyauthors
Long N,Xu X,Zeng Q,Sang H,Lu Ldoi
10.1128/AEM.02924-16subject
Has Abstractpub_date
2017-02-01 00:00:00issue
4eissn
0099-2240issn
1098-5336pii
AEM.02924-16journal_volume
83pub_type
杂志文章abstract::To ascertain its physiological similarity to other methanogenic bacteria, Methanospirillum hungatii, the type species of the genus, was characterized nutritionally and biochemically. Good growth occurred in a medium consisting of mineral salts, cysteine sulfide reducing buffer, and an H2-CO2 (80:20) atmosphere. Additi...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.34.4.371-376.1977
更新日期:1977-10-01 00:00:00
abstract::Our purpose was to develop a rapid, inexpensive method of diagnosing the source of fecal pollution in water. In previous research, we identified Bacteroides-Prevotella ribosomal DNA (rDNA) PCR markers based on analysis. These markers length heterogeneity PCR and terminal restriction fragment length polymorphism distin...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/aem.66.10.4571-4574.2000
更新日期:2000-10-01 00:00:00
abstract::Reductive and oxidative pathways of the sulfur cycle were studied in a marine sediment by parallel radiotracer experiments with SO(4), H(2)S, and S(2)O(3) injected into undisturbed sediment cores. The distributions of viable populations of sulfate- and thiosulfate-reducing bacteria and of thiosulfate-disproportionatin...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.57.3.847-856.1991
更新日期:1991-03-01 00:00:00
abstract::Escherichia coli KO11 was previously constructed to produce ethanol from acid hydrolysates of hemicellulose (pentoses and hexoses) by the chromosomal integration of Zymomonas mobilis genes encoding pyruvate decarboxylase (pdc) and alcohol dehydrogenase (adhB). Klebsiella oxytoca P2 was constructed in an analogous fash...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.63.12.4633-4637.1997
更新日期:1997-12-01 00:00:00
abstract::The kinetics of oxygen reduction by Desulfovibrio salexigens Mast1 and the role of polyglucose in this activity were examined and compared with those of strains of D. desulfuricans and D. gigas. Oxidation rates were highest at air saturation (up to 40 nmol of O(2) min mg of protein) and declined with decreasing oxygen...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.64.3.1034-1039.1998
更新日期:1998-03-01 00:00:00
abstract::Stored sugarbeet roots began fermenting within 24 h after oxygen was depleted at 26 C when the resident bacterial populations increased dramatically. Most of the bacteria present after anaerobic storage for 7 days at 26 C could hydrolyze sucrose in vitro. Although pH and sucrose levels decreased and invert sugar level...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.31.5.754-757.1976
更新日期:1976-05-01 00:00:00
abstract::An agar medium containing 5% cholesterol has been developed for the isolation, enumeration, and characterization of cholesterol-reducing strains of Eubacterium. ...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.40.6.1130-1132.1980
更新日期:1980-12-01 00:00:00
abstract::Four soil temperature and moisture treatment regimens were imposed on Florunner peanuts 94 days after planting in experimental plots in 1980. At harvest (145 days after planting), the incidence of the Aspergillus flavus group and the aflatoxin concentration were greatest in damaged kernels. Extensive colonization of s...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.45.2.628-633.1983
更新日期:1983-02-01 00:00:00
abstract::Quorum sensing (QS) regulates Phaeobacter gallaeciensis antagonism in broth systems; however, we demonstrate here that QS is not important for antagonism in algal cultures. QS mutants reduced Vibrio anguillarum to the same extent as the wild type. Consequently, a combination of probiotic Phaeobacter and QS inhibitors ...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.01436-13
更新日期:2013-09-01 00:00:00
abstract::A gene encoding a new thermostable D-stereospecific alanine amidase from the thermophile Brevibacillus borstelensis BCS-1 was cloned and sequenced. The molecular mass of the purified enzyme was estimated to be 199 kDa after gel filtration chromatography and about 30 kDa on sodium dodecyl sulfate-polyacrylamide gel ele...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/aem.69.2.980-986.2003
更新日期:2003-02-01 00:00:00
abstract::Bacterial strains were isolated on the basis of their ability to proliferate in a minimal medium containing one of a series of lignin-related compounds as the sole carbon and energy source. These included the aromatic monomers guaiacol, vanillic and coumaric acids, a dimer and a trimer possessing the arylglycerol-beta...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.52.6.1428-1432.1986
更新日期:1986-12-01 00:00:00
abstract::Bacillus subtilis induces expression of the gene ytnP in the presence of the antimicrobial streptomycin, produced by the Gram-positive bacterium Streptomyces griseus. ytnP encodes a lactonase-homologous protein that is able to inhibit the signaling pathway required for the streptomycin production and development of ae...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.06992-11
更新日期:2012-01-01 00:00:00
abstract::Four Staphylococcus aureus-Escherichia coli shuttle vectors were constructed for gene expression and production of tagged fusion proteins. Vectors pBUS1-HC and pTSSCm have no promoter upstream of the multiple cloning site (MCS), and this allows study of genes under the control of their native promoters, and pBUS1-Pcap...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.03803-14
更新日期:2015-05-01 00:00:00
abstract::In this study, the feasibility of fluorescence lifetime imaging (FLIM) for measurement of RNA:DNA ratios in microorganisms was assessed. The fluorescence lifetime of a nucleic acid-specific probe (SYTO 13) was used to directly measure the RNA:DNA ratio inside living bacterial cells. In vitro, SYTO 13 showed shorter fl...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.01806-07
更新日期:2008-01-01 00:00:00
abstract::The interactions between dissolved organic matter (DOM) and mineral particles are critical for the stabilization of soil organic matter (SOM) in terrestrial ecosystems. The processing of DOM by ectomycorrhizal fungi contributes to the formation of mineral-stabilized SOM by two contrasting pathways: the extracellular t...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.03007-18
更新日期:2019-05-02 00:00:00
abstract::An inexpensive, simple-to-construct nephelometer which was used to monitor the lysis of spheroplasts is described. The nephelometer is a flow-through device with a linear response to cell concentration from the lower detection limit to 8 x 10(8) cells per ml. ...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.44.6.1476-1478.1982
更新日期:1982-12-01 00:00:00
abstract::Improving access to the carbohydrate content of lignocellulose is key to reducing recalcitrance for microbial deconstruction and conversion to fuels and chemicals. Caldicellulosiruptor bescii completely solubilizes naked microcrystalline cellulose, yet this transformation is impeded within the context of the plant cel...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.00969-17
更新日期:2017-08-17 00:00:00
abstract::When microbes lack the nutrients necessary for growth, they enter stationary phase. In cases when energy sources are still present in the environment, they must decide whether to continue to use their metabolic program to harvest the available energy. Here we characterized the metabolic response to a variety of types ...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.00061-14
更新日期:2014-05-01 00:00:00
abstract::A proteinaceous substance with antibiotic-like activity, resembling that of a bacteriocin, was isolated from an industrial-scale acetone-butanol fermentation of Clostridium acetobutylicum. The substance, purified by acetone precipitation, diethylaminoethyl cellulose chromatography, and polyacrylamide gel electrophores...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.41.2.371-374.1981
更新日期:1981-02-01 00:00:00
abstract::Suspensions of Nitrosomonas europaea catalyzed the oxidation of the commercial nitrification inhibitor nitrapyrin [2-chloro-6-(trichloromethyl)-pyridine]. Rapid oxidation of nitrapyrin (at a concentration of 10 muM) required the concomitant oxidation of ammonia, hydroxylamine, or hydrazine. The turnover rate was highe...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.58.7.2321-2325.1992
更新日期:1992-07-01 00:00:00
abstract::Genome-wide analysis has revealed abundant FabG (beta-ketoacyl-ACP reductase) paralogs, with uncharacterized biological functions, in several halophilic archaea. In this study, we identified for the first time that the fabG1 gene, but not the other five fabG paralogs, encodes the polyhydroxyalkanoate (PHA)-specific ac...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.00938-09
更新日期:2009-10-01 00:00:00
abstract::Vortex flow filtration (VFF) was used to concentrate viruses and dissolved DNA from freshwater and seawater samples taken in Florida, the Gulf of Mexico, and the Bahamas Bank. Recoveries of T2 phage and calf thymus DNA added to artificial seawater and concentrated by VFF were 72.8 and 80%, respectively. Virus concentr...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.57.8.2197-2204.1991
更新日期:1991-08-01 00:00:00
abstract::Methanomicrobium mobile requires a heat-stable factor present in ruminal fluid and in boiled cell extract from Methanobacterium thermoautotrophicum for growth. By comparing the growth of M. mobile with boiled cell extract with that observed with various methanogenic cofactors, we found that 7-mercaptoheptanoylthreonin...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.57.10.2891-2895.1991
更新日期:1991-10-01 00:00:00
abstract::Mycophenolic acid (MPA) is the active ingredient in the increasingly important immunosuppressive pharmaceuticals CellCept (Roche) and Myfortic (Novartis). Despite the long history of MPA, the molecular basis for its biosynthesis has remained enigmatic. Here we report the discovery of a polyketide synthase (PKS), MpaC,...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.03015-10
更新日期:2011-05-01 00:00:00
abstract::Soils harbor enormously diverse bacterial populations, and soil bacterial communities can vary greatly in composition across space. However, our understanding of the specific changes in soil bacterial community structure that occur across larger spatial scales is limited because most previous work has focused on eithe...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.00335-09
更新日期:2009-08-01 00:00:00
abstract::Methylosinus trichosporium OB3b produces an extracellular copper-binding ligand (CBL) with high affinity for copper. Wild-type cells and mutants that express soluble methane monooxygenase (sMMO) in the presence and absence of copper (sMMOc) were used to obtain cell exudates that were separated and analyzed by size exc...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.64.3.1115-1122.1998
更新日期:1998-03-01 00:00:00
abstract::Marine bacteria play a central role in the degradation of dimethylsulfoniopropionate (DMSP) to dimethyl sulfide (DMS) and acrylic acid, DMS being critical to cloud formation and thereby cooling effects on the climate. High concentrations of DMSP and DMS have been reported in scleractinian coral tissues although, to da...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.02567-08
更新日期:2009-06-01 00:00:00
abstract::We applied HNPP (2-hydroxy-3-naphthoic acid-2'-phenylanilide phosphate) to direct in situ PCR for the routine detection of specific bacterial cells at the single-cell level. PCR was performed on glass slides with digoxigenin-labeled dUTP. The digoxigenin-labeled PCR products were detected with alkaline phosphatase-lab...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.64.4.1536-1540.1998
更新日期:1998-04-01 00:00:00
abstract::Since Vibrio cholerae O139 first appeared in 1992, both O1 El Tor and O139 have been recognized as the epidemic serogroups, although their geographic distribution, endemicity, and reservoir are not fully understood. To address this lack of information, a study of the epidemiology and ecology of V. cholerae O1 and O139...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.00066-06
更新日期:2006-06-01 00:00:00
abstract::Biogeochemical transformations occurring in the anoxic zones of stratified sedimentary microbial communities can profoundly influence the isotopic and organic signatures preserved in the fossil record. Accordingly, we have determined carbon isotope discrimination that is associated with both heterotrophic and lithotro...
journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/aem.69.5.2942-2949.2003
更新日期:2003-05-01 00:00:00