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1.
Nikkomycin Z is a specific inhibitor of Saccharomyces cerevisiae chitin synthase isozyme Chs3 in vitro and in vivo. 总被引:6,自引:1,他引:5
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Nikkomycin Z inhibits chitin synthase in vitro but does not exhibit antifungal activity against many pathogens. Assays of chitin synthase isozymes and growth assays with isozyme mutants were used to demonstrate that nikkomycin Z is a selective inhibitor of chitin synthase 3. The resistance of chitin synthase 2 to nikkomycin Z in vitro is likely responsible for the poor activity of this antibiotic against Saccharomyces cerevisiae. 相似文献
2.
Nikkomycin, a nucleoside-peptide analog of UDP-N-acetylglucosamine, is a potent chitin synthase inhibitor produced by the bacterium Streptomyces tendae. The HPLC profile of fermentation products in culture broths of a non-producing mutant, Nik 15, was compared with nikkomycin standards. Nikkomycin C and D, the glycone and aglycone moieties, respectively, of nikkomycin Z accumulated. This indicates the mutation affects the capacity to form a peptide bond between nikkomycin C and D, which is here proposed to be the terminal step in the synthesis of the biologically active nikkomycin Z. This is also the first documented case of a mutation affecting a specific step in nikkomycin biosynthesis. 相似文献
3.
Guojian Liao Jine Li Lei Li Haihua Yang Yuqing Tian Huarong Tan 《Microbial cell factories》2009,8(1):61-7
Background
Nikkomycins are a group of peptidyl nucleoside antibiotics and act as potent inhibitors of chitin synthases in fungi and insects. Nikkomycin X and Z are the main components produced by Streptomyces ansochromogenes. Of them, nikkomycin Z is a promising antifungal agent with clinical significance. Since highly structural similarities between nikkomycin Z and X, separation of nikkomycin Z from the culture medium of S. ansochromogenes is difficult. Thus, generating a nikkomycin Z selectively producing strain is vital to scale up the nikkomycin Z yields for clinical trials. 相似文献4.
J. Haplová V. Farkaš M. Hejtmánek R. Koďousek J. Malínský 《Archives of microbiology》1994,161(4):340-344
Rylux BSU, a new fluorescent brightener from the family of 4,4-diaminostilbene-2,2disulfonic acid derivatives, inhibited growth and cytokinesis of the yeast Saccharomyces cerevisiae. In the presence of 0.1–1 mg/ml Rylux BSU the cells grew in clumps, had irregular shape and were larger than controls. They formed apparently normal primary septa but their secondary septa and lateral cell walls, especially those in older cells, were abnormally thick with large deposits of amorphous wall material in the periplasmic spaces all over the cell surface. Chitin content in the cell walls of cells grown in the presence of Rylux BSU was increased 2 to 5 times in comparison to that of the controls and glucan content was reduced by up to 30%. In the in vitro assays with particulate membrane fractions, Rylux BSU acted as a non-competitive inhibitor of -1,3-glucan synthase with inhibitory constant K
i=1.75 mg/ml whereas the chitin synthase was inhibited to a much lesser extent. From the difference of the effects of Rylux BSU on the synthesis of chitin in vivo and in vitro it is concluded that the brightener interacts with chitin synthase only indirectly, possibly by influencing the properties of integral plasma membrane.Abbreviations RBSU
Rylux BSU, 1,4-benzenedisulfonic acid-2,2-[ethyleneidy]bis[(3-sulpho-4,1-phenylene)imino[6-bis(2-hydroxyethyl)amino]-1,3,5-triazine-4,2-diylamino]]bis-, hexasodium salt
- FB
fluorescent brightener 相似文献
5.
Sensitivity to nikkomycin Z in Candida albicans: role of peptide permeases. 总被引:7,自引:2,他引:5
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The uptake of tritiated nikkomycin Z, a potent inhibitor of chitin synthetase, is mediated by a peptide transport system in Candida albicans. Kinetic transport assays with radioactive di- and tripeptides and competition studies suggest that two distinct systems operate in this yeast. Nikkomycin Z was transported through one of these systems, common to di- and tripeptides. A peptide transport-deficient mutant was isolated on the basis of its resistance to nikkomycin Z. The mutant lost most of its capacity to take up dipeptides but simultaneously increased its ability to transport tripeptides. These results indicate that C. albicans handles peptides through multiple transport systems and adjusts their expression to environmental conditions. 相似文献
6.
Calcofluor-allied optical brightener Rylux BSU stimulated spore germination rate inTrichophyton mentagrophytes andAspergillus fumigatus both if supplemented into Sabouraud glucose agar and if used for pretreatment of spore suspension prior to inoculation at
low concentrations. Maximum stimulation of germination was obtained if 0.2% Rylux BSU was used for pretreatment in aqueous
solution for 1 d prior to inoculation (130% inT. mentagrophytes and 150% inA. fumigatus, respectively). Pretreatment with 1% Rylux BSU provided strong protection against UV-irradiation and resulted in increased
yields of cultural variants after UV-irradiation. 相似文献
7.
Rivera-Molina Félix E. González-Crespo Sahily Cruz Yasdet Maldonado-De la Ortiz-Betancourt José M. Rodríguez-Medina José R. 《World journal of microbiology & biotechnology》2006,22(3):255-260
Summary Nikkomycin Z (NZ) is a competitive inhibitor of chitin synthase III in the yeast Saccharomyces cerevisiae. Myosin type II-deficient yeast strains (myo1) display a dramatic reduction in growth when chitin synthase III activity is inhibited by NZ, supporting the contention that
actomyosin motility plays an important role in maintaining cell wall integrity. A proposed inhibitor of cortical actin polymerization
in vitro, 2,3-butanedione monoxime (BDM), also inhibits growth of wild-type yeast strains at a concentration of 20 mM. In this study,
we assayed for potential in vivo interplay between BDM-sensitive cell functions and cell wall chitin synthesis by testing for increased sensitivity to NZ
during co-treatment with BDM at sub-inhibitory concentrations. Our results show that BDM can increase the sensitivity of yeast
cells to Nikkomycin Z. 相似文献
8.
Spore walls ofBackusella lamprospora (Mucorales) were stained with ten fluorescent brighteners (FB) and the intensity of their fluorescence was determined. The fluorescence
was most intense with Uvitex 2B (100%), other brighteners yielding lower fluorescence intensities: Blankophor BA 267% and
BA 200% about 75%, Rylux BSU about 50%, other Rylux agents 10–30%. The agents most suitable for microscopic diagnostics of
human and animal mycoses are Uvitex 2B, Blankophor BA 267% and BA 200%, Rylux BSU, and also Rylux BS and PRS. The regulation
of excessive fluorescence of fungal cells during microscopic observation is discussed. For the purposes of microscopic diagnosis
of human and animal mycosis Uvitex 2B, Blankophor BA 267% and BA 200%, Rylux BSU and, possibly, Rylux BS and PRS are recommended. 相似文献
9.
尼可霉素是一种新的抗真菌抗生素,在分离到的20多种活性单组分中,X、Z、I、J为主要生物活性组分。本文介绍了尼可霉素的结构,结构与活性的关系及其生物合成途径中有关基因的研究进展。 相似文献
10.
Mechanism of action of nikkomycin and the peptide transport system of Candida albicans 总被引:3,自引:0,他引:3
Nikkomycin was found to be a potent growth inhibitor of Candida albicans through competitive inhibition of chitin synthase [Ki = 0.16 microM (0.1 microgram ml-1)]. The activity of the peptide-nucleoside drug was antagonized by both peptone and defined peptides. Transported dipeptides were effective antagonists while transported oligopeptides were not. A mutant of C. albicans resistant to the effects of nikkomycin through a transport defect was unable to transport dipeptides, while oligopeptide uptake was apparently unaffected. At least two peptide permeases are operational in this organism. 相似文献
11.
Fluconazole, ketoconazole and tioconazole were shown to act synergistically in vitro with the antibiotic nikkomycin X/Z on the pathogenic fungus Candida albicans. The phenomenon was demonstrated using a checkerboard technique and growth inhibition experiments. The azole antifungal agents, even at concentrations not affecting growth, decreased the incorporation of the 14C-label from [14C]glucose into chitin of the candidal cell wall. After 3 h incubation with tioconazole, 1 microgram ml-1, the incorporation of the radiolabelled glucose into chitin of intact cells and regenerating spheroplasts of C. albicans was inhibited by 43% and 30%, respectively. Moreover, the relative chitin content was approximately 45% lower than that of control cells. The chitin content increased after prolonged incubation with azoles, thus confirming the known phenomenon of azole-induced uncoordinated chitin synthesis and deposition. On the other hand, azole derivatives had very little effect on the rate of nikkomycin transport into C. albicans cells. A sequential blockade mechanism of synergism is proposed. 相似文献
12.
Hill TW Loprete DM Momany M Ha Y Harsch LM Livesay JA Mirchandani A Murdock JJ Vaughan MJ Watt MB 《Mycologia》2006,98(3):399-409
As a first step toward identifying novel genes of wall metabolism in filamentous fungi, we have screened a collection of Aspergillus nidulans mutants for strains exhibiting hypersensitivity toward the chitin binding agent Calcofluor White (CFW). This strategy has been used previously to identify cell wall mutants in Saccharomyces cerevisiae. We have identified 10 mutants representing eight loci, designated calA through calH, for Calcofluor hypersensitivity. All cal mutants are impaired for sporulation at 30 C or 42 C or both, and in eight of the 10 mutations this sporulation defect shows at least partial osmotic remediability. All cal mutants show elevated sensitivity to one or more of the following agents: Caspofungin, Nikkomycin, Tunicamycin, Congo red and SDS, which are recognized wall-compromising agents or have been shown to be inhibitory to wall integrity mutants in yeast. Seven of the 10 cal mutants show swelling at elevated temperature, which in most cases is osmotically remediable. Spore swelling also can be induced at 30 C in all but one of the cal mutants by germination in the presence of one or more of the following: Caspofungin, Nikkomycin or Tunicamycin. Analysis of wall sugars showed no major changes in mutant strains. We also report that the chitin synthase inhibitor Nikkomycin induces excessive spore swelling during germination in all tested strains that have wild type cell wall metabolism (GR5, A4, A28 and AH12) at 42 C but not at 30 C. This effect mimics that of certain temperature-sensitive swollen cell (swo) mutations. 相似文献
13.
Beatriz Cubero José Ruiz-Herrera Enrique Cerdá-Olmedo 《Molecular & general genetics : MGG》1993,240(1):9-16
Mutants resistant to nikkomycin, an inhibitor of chitin biosynthesis, were isolated after exposure of wild-type spores of the fungus Phycomyces blakesleeanus to N-methyl-N-nitro-N-nitrosoguanidine. Genetic analysis revealed that nikkomycin resistance was due to mutations in a single gene, chsA. Mutants and wild type grew equally well in the absence of nikkomycin. In contrast to the wild type, whose spore germination and mycelial growth were inhibited by 5 M nikkomycin, chsA mutants grew reasonably well in the presence of 50 M nikkomycin. Chitin synthesis in vivo was much less affected by the drug in the mutants than in the wild type. Resistance was not due to impaired uptake or detoxification of the drug. Analysis of the kinetics of chitin synthesis in vitro showed that the mutants had a decreased Ka for the allosteric activator, N-acetylglucosamine, and gross alterations in nikkomycin inhibition kinetics. These results indicate that chsA is the structural gene for chitin synthetase, or at least for the polypeptide that bears the catalytic and allosteric sites. 相似文献
14.
H. Matsuoka H.-C. Yang T. Homma Y. Nemoto S. Yamada O. Sumita K. Takatori H. Kurata 《Applied microbiology and biotechnology》1995,43(1):102-108
Congo red was found to be feasible as a microscopic fluorescence indicator of hyphal growth at the single-hypha level. When 1 m Congo red was applied to mold of Aspergillus niger, the dye was found to a specific cell-wall component, chitin, without causing any inhibitory effect on hyphal growth. The bound Congo red emitted fluorescence at 614 nm. This binding reaction, however, proceeded more slowly than the growing speed of hypha. Consequently the fluorescence intensity was low at the apex where the surface area of the hypha was expanding rapidly. In contrast, as an apex where the growth was retarded, the fluorescence intensity became remarkably high. Therefore growing hyphae could be distinguished from non-growing hyphae by using Congo red. 相似文献
15.
Ulrich Schlüter 《Development genes and evolution》1982,191(3):205-207
Summary The nucleoside antibiotic nikkomycin has proved to be an effective inhibitor of chitin synthesis in the Mexican bean beetleEpilachna varivestis. Ultrastructural investigations show defects in the procuticular area after nikkomycin application which suggest the complete absence of chitin. A cuticle like this is inflexible and too brittle to satisfy its normal function as an exoskeleton. The individuals are not able to free themselves from the exuvia and finally die. Therefore nikkomycin seems to be a potential insecticide with high specifity. 相似文献
16.
A novel mode of reversed-phase high-performance liquid chromatography in which the mobile phase reacts chemically with the compounds to be separated was developed. Nikkomycin X and nikkomycin Z, two natural isomeric nucleoside peptide antibiotics, move as a single peak on a C18 reversed-phase column using an aqueous trifluoroacetic acid mobile phase. Addition of sodium bisulfite (1.0%) to the mobile phase results in the formation of a polar bisulfite addition product with nikkomycin X, but not with nikkomycin Z, inside the HPLC column. This type of reactive chromatography, or chemochromatography, led to the analytical and preparative separation of nikkomycins X and Z which are normally very intractable to separation by conventional chromatographic techniques. 相似文献
17.
Beatriz Cubero José Ruiz-Herrera Enrique Cerdá-Olmedo 《Molecular genetics and genomics : MGG》1993,240(1):9-16
Mutants resistant to nikkomycin, an inhibitor of chitin biosynthesis, were isolated after exposure of wild-type spores of the fungus Phycomyces blakesleeanus to N-methyl-N′-nitro-N-nitrosoguanidine. Genetic analysis revealed that nikkomycin resistance was due to mutations in a single gene, chsA. Mutants and wild type grew equally well in the absence of nikkomycin. In contrast to the wild type, whose spore germination and mycelial growth were inhibited by 5 μM nikkomycin, chsA mutants grew reasonably well in the presence of 50 μM nikkomycin. Chitin synthesis in vivo was much less affected by the drug in the mutants than in the wild type. Resistance was not due to impaired uptake or detoxification of the drug. Analysis of the kinetics of chitin synthesis in vitro showed that the mutants had a decreased Ka for the allosteric activator, N-acetylglucosamine, and gross alterations in nikkomycin inhibition kinetics. These results indicate that chsA is the structural gene for chitin synthetase, or at least for the polypeptide that bears the catalytic and allosteric sites. 相似文献
18.
Cell wall integrity is crucial for fungal growth, development and stress survival. In the model yeast Saccharomyces cerevisiae, the cell integrity Mpk1/Slt2 MAP kinase and calcineurin pathways monitor cell wall integrity and promote cell wall remodelling under stress conditions. We have identified the Cryptococcus neoformans homologue of the S. cerevisiae Mpk1/Slt2 MAP kinase and have characterized its role in the maintenance of cell integrity in response to elevated growth temperature and in the presence of cell wall synthesis inhibitors. C. neoformans Mpk1 is required for growth at 37 degrees C in vitro, and this growth defect is suppressed by osmotic stabilization. C. neoformans mutants lacking Mpk1 are attenuated for virulence in the mouse model of cryptococcosis. Phosphorylation of Mpk1 is induced in response to perturbations of cell wall biosynthesis by the antifungal drugs nikkomycin Z (a chitin synthase inhibitor), caspofungin (a beta-1,3-glucan synthase inhibitor), or FK506 (a calcineurin inhibitor), and mutants lacking Mpk1 display enhanced sensitivity to nikkomycin Z and caspofungin. Lastly, we show that calcineurin and Mpk1 play complementing roles in regulating cell integrity in C. neoformans. Our studies demonstrate that pharmacological inhibition of the cell integrity pathway would enhance the activity of antifungal drugs that target the cell wall. 相似文献
19.
20.
Guojian Liao Jine Li Lei Li Haihua Yang Yuqing Tian Huarong Tan 《Microbial cell factories》2010,9(1):6