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991.
992.
Turk S Verlaine O Gerards T Zivec M Humljan J Sosič I Amoroso A Zervosen A Luxen A Joris B Gobec S 《PloS one》2011,6(5):e19418
Background
Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs β-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for β-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs.Methodology/Principal Findings
Our in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains.Conclusions
We found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria. 相似文献993.
Catabolism of Pyrimidines in Rape Seedlings 总被引:4,自引:0,他引:4
994.
995.
Griphin Ochieng Ochola Bei Li Vincent Obanda Sheila Ommeh Harold Ochieng Xing-Lou Yang Samson Omondi Onyuok Zheng-Li Shi Bernard Agwanda Ben Hu 《中国病毒学》2022,37(4):491-502
Emergence and re-emergence of infectious diseases of wildlife origin have led pre-emptive pathogen surveillances in animals to be a public health priority. Rodents and shrews are among the most numerically abundant vertebrate taxa and are known as natural hosts of important zoonotic viruses. Many surveillance programs focused more on RNA viruses. In comparison, much less is known about DNA viruses harbored by these small mammals. To fill this knowledge gap, tissue specimens of 232 animals including 226 rodents, five shrews and one hedgehog were collected from 5 counties in Kenya and tested for the presence of DNA viruses belonging to 7 viral families by PCR. Diverse DNA sequences of adenoviruses, adeno-associated viruses, herpesviruses and polyomaviruses were detected. Phylogenetic analyses revealed that most of these viruses showed distinction from previously described viruses and formed new clusters. Furthermore, this is the first report of the discovery and full-length genome characterization of a polyomavirus in Lemniscomys species. This novel polyomavirus, named LsPyV KY187, has less than 60% amino acid sequence identity to the most related Glis glis polyomavirus 1 and Sciurus carolinensis polyomavirus 1 in both large and small T-antigen proteins and thus can be putatively allocated to a novel species within Betapolyomavirus. Our findings help us better understand the genetic diversity of DNA viruses in rodent and shrew populations in Kenya and provide new insights into the evolution of those DNA viruses in their small mammal reservoirs. It demonstrates the necessity of ongoing pathogen discovery studies targeting rodent-borne viruses in East Africa. 相似文献
996.
Lineage-specific expression of c-fos and c-fms in human hematopoietic cells: Discrepancies with the in vitro differentiation of leukemia cells 总被引:2,自引:0,他引:2
Hans Kreipe Heinz J. Radzun Klaus Heidorn Mohammad Reza Parwaresch Bernard Verrier Rolf Müller 《Differentiation; research in biological diversity》1986,33(1):56-60
In vitro differentiation studies using the bipotential human leukemia cell line, HL60, have indicated that high levels of expression of two proto-oncogenes, c-fos and c-fms, are restricted to the myelomonocytic lineage. No such expression has been detected in induced granulocytic cells. In striking contrast to these observations, we found that c-fos mRNA levels are very high in purified human granulocytes, but barely detectable in blood monocytes and tissue macrophages. Human granulocytes contain, however, relatively low levels of c-fos protein, indicating that c-fos mRNA is inefficiently translated or that the protein is rapidly degraded in these cells. In closer agreement with the in vitro results, the level of the expression of c-fms is high in purified blood monocytes and undetectable in granulocytes. We found, however, that the evolution of monocytes into tissue macrophages is accompanied by a significant decrease in c-fms expression, suggesting that the function of c-fms is restricted to specific stages of monocytic differentiation. Our observations also show that results obtained using in vitro differentiation systems have to be regarded with caution, since they may not reflect the in vivo situation. 相似文献
997.
998.
999.
Geomorphic influence on intraspecific genetic differentiation and diversity along hyporheic corridors 下载免费PDF全文
Florian Malard Cécile Capderrey Benjamin Churcheward David Eme Bernard Kaufmann Lara Konecny‐Dupré Jean‐Paul Léna Frédéric Liébault Christophe J. Douady 《Freshwater Biology》2017,62(12):1955-1970
1000.
Nicolas Bouquin Mao X. Chen Sunghoon Kim Françoise Vannier Sylvie Bernard I. Barry Holland Simone J. Séror 《Molecular microbiology》1996,20(4):853-865
We previously described a mutation feeB1 conferring a temperature-sensitive filamentation phenotype and resistance to the calmodulin inhibitor 48/80 in Escherichia coli, which constitutes a single base change in the acceptor stem of the rare tRNA3Leu recognizing CUA codons. We now describe a second mutant, feeA1, unlinked to feeB, but displaying a similar phenotype, 48/80 resistance and a reduced growth rate at the permissive temperature, 30°C, and temperature-sensitive, forming short filaments at 42°C. In the feeA mutant, tRNA3Leu expression (but not that of tRNA1Leu) was reduced approximately fivefold relative to the wild type. We previously showed that the synthesis of β-galactosidase, which unusually requires the translation of 6-CUA codons, was substantially reduced, particularly at 42°C, in feeB mutants. The feeA mutant also shows drastically reduced synthesis of β-galactosidase at the non-permissive temperature and reduced levels even at the permissive temperature. We also show that increased copy numbers of the abundant tRNA1Leu, which can also read CUA codons at low efficiency, suppressed the effects of feeA1 under some conditions, providing further evidence that the mutant was deficient in CUA translation. This, and the previous study, demonstrates that mutations which either reduce the activity of tRNA3Leu or the cellular amount of tRNA3Leu confer resistance to the drug 48/80, with concomitant inhibition of cell division at 42°C. 相似文献