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排序方式: 共有176条查询结果,搜索用时 31 毫秒
91.
Anne-Marie Bencivengo Mare Cudic Ralf Hoffmann Laszlo Otvos Jr 《Letters in Peptide Science》2001,8(3-5):201-209
Pyrrhocoricin, a highly active antibacterial peptide isolated from insects, inhibits chaperone-assisted protein folding via binding to the 70 kDa heat shock protein DnaK with its amino terminal half. The C-terminus functions as an intracellular delivery module. In the current study, chimeras consisting of the putative functional units of pyrrhocoricin and a related peptide, drosocin, were made, and it was found that some mixed and matched sequences retained their ability to kill Escherichia coli, Salmonella typhimurium and Agrobacterium tumefaciens. While pyrrhocoricin appeared to have a more universal pharmacophore, drosocin featured a more robust intracellular delivery unit. We also identified the minimal length of pyrrhocoricin that is needed to efficiently kill bacteria. While for activity against S. typhimurium the peptide could not be shortened, against E. coli it was sufficient to have a Val1-Ile16 amino-terminal fragment. Although Val1 was not part of the Asp2-Pro10 pharmacophore (it could be replaced with other residues), it could not be eliminated and apparently played an important role in defining the activity of the peptide. Indeed, when Val1 was replaced with lysine, not only the efficacy of pyrrhocoricin to kill the sensitive strains increased significantly, resulting in the most active antimicrobial peptide against some clinical strains ever made, but the modified peptide was also able to kill Pseudomonas aeruginosa, an originally unresponsive bacterium in the low g ml-1 concentration range. However, this substitution likely influenced the interaction with bacterial membranes rather than that with the target protein, and therefore the dominant mode of action of the Lys1-pyrrhocoricin peptide may feature membrane disintegration instead of DnaK inhibition. 相似文献
92.
Development of novel antibacterial peptides that kill resistant isolates 总被引:13,自引:0,他引:13
Cudic M Condie BA Weiner DJ Lysenko ES Xiang ZQ Insug O Bulet P Otvos L 《Peptides》2002,23(12):2071-2083
The rapid emergence of bacterial strains that are resistant to current antibiotics requires the development of novel types of antimicrobial compounds. Proline-rich cationic antibacterial peptides such as pyrrhocoricin kill responsive bacteria by binding to the 70 kDa heat shock protein DnaK and inhibiting protein folding. We designed and synthesized multiply protected dimeric analogs of pyrrhocoricin and optimized the in vitro antibacterial efficacy assays for peptide antibiotics. Pyrrhocoricin and the designed dimers killed β-lactam, tetracycline- or aminoglycoside-resistant strains of Escherichia coli, Salmonella typhimurium, Klebsiella pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the submicromolar or low micromolar concentration range. One of the peptides also killed Pseudomonas aeruginosa. The designed dimers showed improved stability in mammalian sera compared to the native analog. In a murine H. influenzae lung infection model, a single dose of a dimeric pyrrhocoricin analog reduced the bacteria in the bronchoalveolar lavage when delivered intranasally. The solid-phase synthesis was optimized for large-scale laboratory preparations. 相似文献
93.
Seven species ofBucania Hall 1847 from the Ordovician of Estonia are presented, also taking into consideration Pleistocene drift material from Germany, and their stratigraphical and geographical distributions are revised. The Middle Ordovician speciesBucania latissima Koken 1897 andBucania salpinx Koken 1897 are tentatively assigned toMegalomphala Ulrich inUlrich &Scofield 1897, while the Lower Ordovician speciesBucania macera Koken inKoken &Perner 1925 is placed inSalpingostoma Roemer 1876. The Middle OrdovicianBucania czekanowskii (Schmidt 1858) and the Upper OrdovicianBucania radiata (d’Eichwald 1856) were earlier considered conspecific, but based on study of the type material they are here considered distinct species.Salpingostoma cornu (Koken 1897), commonly referred to this genus because of the trema, is here transferred toBucania. Two Upper Ordovician specimens ofBucania display wide and abruptly flaring apertures morphologically far removed from other species of the genus. 相似文献
94.
95.
Jirkovská M Majer F Smídová J Stríteský J Shaik GM Dráber P Vítek L Marecek Z Smíd F 《Glycoconjugate journal》2007,24(4-5):231-241
(Glyco)sphingolipids (GSL) are believed to protect the cell against harmful environmental factors by increasing the rigidity
of plasma membrane. Marked decrease of membrane fluidity in cholestatic hepatocytes was described but the role of GSL therein
has not been investigated so far. In this study, localization in hepatocytes of a representative of GSL, the GM1 ganglioside,
was compared between of rats with cholestasis induced by 17α-ethinylestradiol (EE) and vehicle propanediol treated or untreated
animals. GM1 was monitored by histochemical reaction employing cholera toxin B-subunit. Our findings in normal rat liver tissue
showed that GM1 was localized in sinusoidal and canalicular hepatocyte membranes in both peripheral and intermediate zones
of the hepatic lobules, and was nearly absent in central zones. On the contrary, in EE-treated animals GM1 was also expressed
in central lobular zones. Moreover, detailed densitometry analysis at high magnification showed greater difference of GM1
expression between sinusoidal surface areas and areas of adjacent cytoplasm, caused as well by increased sinusoidal staining
in central lobular zone as by decreased staining in cytoplasm in peripheral zone. These differences correlated with serum
bile acids as documented by linear regression analyses. Both GM1 content and mRNA corresponding to GM1-synthase remained unchanged
in livers; the enhanced expression of GM1 at sinusoidal membrane thus seems to be due to re-distribution of cellular GM1 at
limited biosynthesis and could be responsible for protection of hepatocytes against harmful effects of bile acids accumulated
during cholestasis. 相似文献
96.
Phylogenetic analysis of cultivation‐resistant terrestrial cyanobacteria with massive sheaths (Stigonema spp. and Petalonema alatum,Nostocales, Cyanobacteria) using single‐cell and filament sequencing of environmental samples 下载免费PDF全文
Jan Mareš Yannick Lara Iva Dadáková Tomáš Hauer Bohuslav Uher Annick Wilmotte Jan Kaštovský 《Journal of phycology》2015,51(2):288-297
Molecular assessment of a large portion of traditional cyanobacterial taxa has been hindered by the failure to isolate and grow them in culture. In this study, we developed an optimized protocol for single cell/filament isolation and 16S rRNA gene sequencing of terrestrial cyanobacteria with large mucilaginous sheaths, and applied it to determine the phylogenetic position of typical members of the genera Petalonema and Stigonema. A methodology based on a glass‐capillary isolation technique and a semi‐nested PCR protocol enabled reliable sequencing of the 16S rRNA gene from all samples analyzed. Ten samples covering seven species of Stigonema from Europe, North and Central America, and Hawaii, and the type species of Petalonema from Slovakia were sequenced. Contrary to some previous studies, which proposed a relationship with heteropolar nostocalean cyanobacteria, Petalonema appeared to belong to the family Scytonemataceae. Analysis of Stigonema specimens recovered a unique coherent phylogenetic cluster, substantially broadening our knowledge of the molecular diversity within this genus. Neither the uni‐ to biseriate species nor the multiseriate species formed monophyletic subclusters within the genus. Typical multiseriate species of Stigonema clustered in a phylogenetic branch derived from uni‐ to biseriate S. ocellatum Thuret ex Bornet & Flahault in our analysis, suggesting that species with more complex thalli may have evolved from the more simple ones. We propose the technique tested in this study as a promising tool for a future revision of the molecular taxonomy in cyanobacteria. 相似文献
97.
A combined morphological,ultrastructural, molecular,and biochemical study of the peculiar family Gomontiellaceae (Oscillatoriales) reveals a new cylindrospermopsin‐producing clade of cyanobacteria 下载免费PDF全文
Markéta Bohunická Jan Mareš Pavel Hrouzek Petra Urajová Martin Lukeš Jan Šmarda Jiří Komárek Lira A. Gaysina Otakar Strunecký 《Journal of phycology》2015,51(6):1040-1054
Members of the morphologically unusual cyanobacterial family Gomontiellaceae were studied using a polyphasic approach. Cultured strains of Hormoscilla pringsheimii, Starria zimbabweënsis, Crinalium magnum, and Crinalium epipsammum were thoroughly examined, and the type specimen of the family, Gomontiella subtubulosa, was investigated. The results of morphological observations using both light microscopy and transmission electron microscopy were consistent with previous reports and provided evidence for the unique morphological and ultrastructural traits of this family. Analysis of the 16S rRNA gene confirmed the monophyletic origin of non‐marine repre‐sentatives of genera traditionally classified into this family. The family was phylogenetically placed among other groups of filamentous cyanobacterial taxa. The presence of cellulose in the cell wall was analyzed and confirmed in all cultured Gomontiellaceae members using Fourier transform infrared spectroscopy and fluorescence microscopy. Evaluation of toxins produced by the studied strains revealed the hepatotoxin cylindrospermopsin (CYN) in available strains of the genus Hormoscilla. Production of this compound in both Hormoscilla strains was detected using high‐performance liquid chromatography in tandem with high resolution mass spectrometry and confirmed by positive PCR amplification of the cyrJ gene from the CYN biosynthetic cluster. To our knowledge, this is the first report of CYN production by soil cyanobacteria, establishing a previously unreported CYN‐producing lineage. This study indicates that cyanobacteria of the family Gomontiellaceae form a separate but coherent cluster defined by numerous intriguing morphological, ultrastructural, and biochemical features, and exhibiting a toxic potential worthy of further investigation. 相似文献
98.
Goran Kragol Ralf Hoffmann Michael A Chattergoon Sandor Lovas Mare Cudic Philippe Bulet Barry A Condie K Johan Rosengren Luis J Montaner Laszlo Otvos 《European journal of biochemistry》2002,269(17):4226-4237
Members of the proline-rich antibacterial peptide family, pyrrhocoricin, apidaecin and drosocin appear to kill responsive bacterial species by binding to the multihelical lid region of the bacterial DnaK protein. Pyrrhocoricin, the most potent among these peptides, is nontoxic to healthy mice, and can protect these animals from bacterial challenge. A structure-antibacterial activity study of pyrrhocoricin against Escherichia coli and Agrobacterium tumefaciens identified the N-terminal half, residues 2-10, the region responsible for inhibition of the ATPase activity, as the fragment that contains the active segment. While fluorescein-labeled versions of the native peptides entered E. coli cells, deletion of the C-terminal half of pyrrhocoricin significantly reduced the peptide's ability to enter bacterial or mammalian cells. These findings highlighted pyrrhocoricin's suitability for combating intracellular pathogens and raised the possibility that the proline-rich antibacterial peptides can deliver drug leads into mammalian cells. By observing strong relationships between the binding to a synthetic fragment of the target protein and antibacterial activities of pyrrhocoricin analogs modified at strategic positions, we further verified that DnaK was the bacterial target macromolecule. Inaddition, the antimicrobial activity spectrum of native pyrrhocoricin against 11 bacterial and fungal strains and the binding of labeled pyrrhocoricin to synthetic DnaK D-E helix fragments of the appropriate species could be correlated. Mutational analysis on a synthetic E. coli DnaK fragment identified a possible binding surface for pyrrhocoricin. 相似文献
99.
Helena Marešová Martina Plačková Michal Grulich Pavel Kyslík 《Applied microbiology and biotechnology》2014,98(7):2867-2879
In the course of more than 60-year history, penicillin G acylase (PGA) gained a unique position among enzymes used by pharmaceutical industry for production of β-lactam antibiotics. Kinetically controlled enzymatic syntheses of cephalosporins of novel generations in which PGA catalyzes coupling of activated acyl donor with nucleophile belong among the latest large-scale applications. Contrary to rather specific roles of other enzymes involved in β-lactam biocatalyses, the PGA seems to have the greatest potential. On the laboratory scale, other applications with industrial potential were described, e.g., directed evolution of the enzyme to meet specific demands of industrial processes or its modification into the enzyme catalyzing reactions with novel substrates. The fact that β-lactams represent the most important group of antibiotics comprising 65 % of the world antibiotic market explains such a tremendous and continuous interest in this enzyme. Indeed, the annual consumption of PGA has recently been estimated to range from 10 to 30 million tons. The application potential of the enzyme goes beyond the β-lactam biocatalysis due to its enantioselectivity and promiscuity: the PGA can be used for the production of achiral and chiral compounds convenient for the preparation of synthons and active pharmaceutical ingrediences, respectively. These biocatalyses, however, still wait for large-scale application. 相似文献
100.
Variation in the fire-survival strategy of the fynbos, legume tribesPodalyrieae andLiparieae was studied, since it is often the only conspicuous difference between morphologically similar taxa. Two main strategies are apparent: sprouters, taxa which are able to sprout from a woody rootstock after fire and non-sprouters, those which only recruit from seed after fire. In fynbos legumes sprouting and non-sprouting taxa differ in their habitat specificity, population densities, relative regional abundance, and in seed germination tempo. Speciation patterns, as inferred from an analysis of the geographical distribution and habitat specificity of the species, are discussed. Problems relating to the use of sprouting versus non-sprouting as a taxonomic character in fynbos legumes are addressed and possible solutions are given. 相似文献