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1.
Bacterial resistance to beta-lactam antibiotics: crystal structure of beta-lactamase from Staphylococcus aureus PC1 at 2.5 A resolution 总被引：28，自引：0，他引：28
beta-lactamases are enzymes that protect bacteria from the lethal effects of beta-lactam antibiotics, and are therefore of considerable clinical importance. The crystal structure of beta-lactamase from the Gram-positive bacterium Staphylococcus aureus PC1 has been determined at 2.5 angstrom resolution. It reveals a molecule of novel topology, made up of two closely associated domains. The active site is located at the interface between the domains, with the key catalytic residue Ser70 at the amino terminus of a buried helix. Examination of the disposition of the functionally important residues within the active site depression leads to a model for the binding of a substrate and a functional analogy to the serine proteases. The unusual topology of the secondary structure units is relevant to questions concerning the evolutionary relation to the beta-lactam target enzymes of the bacterial cell wall. 相似文献
2.
Coordinate regulation of beta-lactamase induction and peptidoglycan composition by the amp operon 总被引：5，自引：0，他引：5
E Tuomanen S Lindquist S Sande M Galleni K Light D Gage S Normark 《Science (New York, N.Y.)》1991,251(4990):201-204
The amp operon, which is located on the Escherichia coli chromosome, modulates the induction of plasmid-borne beta-lactamase genes by extracellular beta-lactam antibiotics. This suggests that the gene products AmpD and AmpE may function in the transduction of external signals. beta-Lactam antibiotics are analogs of cell wall components that can be released during cell wall morphogenesis of enterobacteria. The amp operon was studied to determine its importance in signal transduction during cell wall morphogenesis. The peptidoglycan compositions of amp mutants were determined by high-performance liquid chromatography and fast atom bombardment mass spectrometry. When a chromosomal or plasmid-borne copy of ampD was present, the amount of pentapeptide-containing muropeptides in the cell wall increased upon addition of the cell wall constituent diaminopimelic acid to the growth medium. These results suggest that beta-lactamase induction and modulation of the composition of the cell wall share elements of a regulatory circuit that involves AmpD. Escherichia coli requires AmpD to respond to extracellular signaling amino acids, such as diaminopimelic acid, and this signal transduction system may regulate peptidoglycan composition in response to cell wall turnover products. 相似文献
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4.
Mitochondria and chloroplasts are essential eukaryotic organelles of endosymbiotic origin. Dynamic cellular machineries divide these organelles. The mechanisms by which mitochondria and chloroplasts divide were thought to be fundamentally different because chloroplasts use proteins derived from the ancestral prokaryotic cell division machinery, whereas mitochondria have largely evolved a division apparatus that lacks bacterial cell division components. Recent findings indicate, however, that both types of organelles universally require dynamin-related guanosine triphosphatases to divide. This mechanistic link provides fundamental insights into the molecular events driving the division, and possibly the evolution, of organelles in eukaryotes. 相似文献
5.
促生细菌的挥发性有机物可以促进拟南芥生长,提高拟南芥对多种生物和非生物胁迫的抗性。近年来的研究表明,植物lncRNA参与生长、发育和胁迫反应等生理过程。通过去rRNA全转录组测序,筛选出受到根际促生细菌ACCC 01380挥发性有机物处理影响的拟南芥lncRNA,并通过顺式分析获得可能受到这些lncRNA调控的蛋白编码基因;通过ceRNA分析获得lncRNA影响蛋白编码基因表达的调控网络。结果发现,拟南芥重要的生长发育调控和胁迫响应基因,如细胞分裂素降解基因At CKX7、SOS2-like protein kinase PKS5,都受到促生细菌的挥发性有机物通过lncRNA的调控。研究结果初步证实了根际促生细菌挥发性有机物在促生过程中lncRNA的作用,并为进一步研究lncRNA功能以及根际促生细菌挥发性有机物的作用机理奠定了基础。 相似文献
6.
The RAD9 gene controls the cell cycle response to DNA damage in Saccharomyces cerevisiae 总被引：128，自引：0，他引：128
Cell division is arrested in many organisms in response to DNA damage. Examinations of the genetic basis for this response in the yeast Saccharomyces cerevisiae indicate that the RAD9 gene product is essential for arrest of cell division induced by DNA damage. Wild-type haploid cells irradiated with x-rays either arrest or delay cell division in the G2 phase of the cell cycle. Irradiated G1 and M phase haploid cells arrest irreversibly in G2 and die, whereas irradiated G2 phase haploid cells delay in G2 for a time proportional to the extent of damage before resuming cell division. In contrast, irradiated rad9 cells in any phase of the cycle do not delay cell division in G2, but continue to divide for several generations and die. However, efficient DNA repair can occur in irradiated rad9 cells if irradiated cells are blocked for several hours in G2 by treatment with a microtubule poison. The RAD9-dependent response detects potentially lethal DNA damage and causes arrest of cells in G2 until such damage is repaired. 相似文献
7.
Sherratt DJ 《Science (New York, N.Y.)》2003,301(5634):780-785
Bacterial chromosomes are highly compacted structures and share many properties with their eukaryote counterparts, despite not being organized into chromatin or being contained within a cell nucleus. Proteins conserved across all branches of life act in chromosome organization, and common mechanisms maintain genome integrity and ensure faithful replication. The principles that underlie chromosome segregation in bacteria and eukaryotes share similarities, although bacteria segregate DNA as it replicates and lack a eukaryote-like mitotic apparatus for segregating chromosomes. This may be because the distances that newly replicated bacterial chromosomes move apart before cell division are small as compared to those in eukaryotes. Bacteria specify positional information, which determines where cell division will occur and which places the replication machinery and chromosomal loci at defined locations that change during cell cycle progression. 相似文献
8.
Haydon DJ Stokes NR Ure R Galbraith G Bennett JM Brown DR Baker PJ Barynin VV Rice DW Sedelnikova SE Heal JR Sheridan JM Aiwale ST Chauhan PK Srivastava A Taneja A Collins I Errington J Czaplewski LG 《Science (New York, N.Y.)》2008,321(5896):1673-1675
FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian beta-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug-resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy. 相似文献
9.
Hasper HE Kramer NE Smith JL Hillman JD Zachariah C Kuipers OP de Kruijff B Breukink E 《Science (New York, N.Y.)》2006,313(5793):1636-1637
Lantibiotics are polycyclic peptides containing unusual amino acids, which have binding specificity for bacterial cells, targeting the bacterial cell wall component lipid II to form pores and thereby lyse the cells. Yet several members of these lipid II-targeted lantibiotics are too short to be able to span the lipid bilayer and cannot form pores, but somehow they maintain their antibacterial efficacy. We describe an alternative mechanism by which members of the lantibiotic family kill Gram-positive bacteria by removing lipid II from the cell division site (or septum) and thus block cell wall synthesis. 相似文献
10.
Beech PL Nheu T Schultz T Herbert S Lithgow T Gilson PR McFadden GI 《Science (New York, N.Y.)》2000,287(5456):1276-1279
A homolog of the bacterial cell division gene ftsZ was isolated from the alga Mallomonas splendens. The nuclear-encoded protein (MsFtsZ-mt) was closely related to FtsZs of the alpha-proteobacteria, possessed a mitochondrial targeting signal, and localized in a pattern consistent with a role in mitochondrial division. Although FtsZs are known to act in the division of chloroplasts, MsFtsZ-mt appears to be a mitochondrial FtsZ and may represent a mitochondrial division protein. 相似文献
11.
Ge M Chen Z Onishi HR Kohler J Silver LL Kerns R Fukuzawa S Thompson C Kahne D 《Science (New York, N.Y.)》1999,284(5413):507-511
Vancomycin is an important drug for the treatment of Gram-positive bacterial infections. Resistance to vancomycin has begun to appear, posing a serious public health threat. Vancomycin analogs containing modified carbohydrates are very active against resistant microorganisms. Results presented here show that these carbohydrate derivatives operate by a different mechanism than vancomycin; moreover, peptide binding is not required for activity. It is proposed that carbohydrate-modified vancomycin compounds are effective against resistant bacteria because they interact directly with bacterial proteins involved in the transglycosylation step of cell wall biosynthesis. These results suggest new strategies for designing glycopeptide antibiotics that overcome bacterial resistance. 相似文献
12.
Aldridge BB Fernandez-Suarez M Heller D Ambravaneswaran V Irimia D Toner M Fortune SM 《Science (New York, N.Y.)》2012,335(6064):100-104
Cells use both deterministic and stochastic mechanisms to generate cell-to-cell heterogeneity, which enables the population to better withstand environmental stress. Here we show that, within a clonal population of mycobacteria, there is deterministic heterogeneity in elongation rate that arises because mycobacteria grow in an unusual, unipolar fashion. Division of the asymmetrically growing mother cell gives rise to daughter cells that differ in elongation rate and size. Because the mycobacterial cell division cycle is governed by time, not cell size, rapidly elongating cells do not divide more frequently than slowly elongating cells. The physiologically distinct subpopulations of cells that arise through asymmetric growth and division are differentially susceptible to clinically important classes of antibiotics. 相似文献
13.
Nguyen D Joshi-Datar A Lepine F Bauerle E Olakanmi O Beer K McKay G Siehnel R Schafhauser J Wang Y Britigan BE Singh PK 《Science (New York, N.Y.)》2011,334(6058):982-986
Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections. 相似文献
14.
Genetic engineering of filamentous fungi 总被引：12，自引：0，他引：12
Filamentous fungi are important in medicine, industry, agriculture, and basic biological research. For example, some fungal species are pathogenic to humans, whereas others produce beta-lactam antibiotics (penicillin and cephalosporin). Industrial strains produce large amounts of enzymes, such as glucoamylase and proteases, and low molecular weight compounds, such as citric acid. The largest and most economically important group of plant pathogens are fungi. Several fungal species have biological properties and genetic systems that make them ideally suited for basic biological research. Recently developed techniques for genetic engineering of filamentous fungi make it possible to alter their detrimental and beneficial activities in novel ways. 相似文献
15.
FtsZ is a tubulin homolog and the major cytoskeletal protein in bacterial cell division. It assembles into the Z ring, which contains FtsZ and a dozen other division proteins, and constricts to divide the cell. We have constructed a membrane-targeted FtsZ (FtsZ-mts) by splicing an amphipathic helix to its C terminus. When mixed with lipid vesicles, FtsZ-mts was incorporated into the interior of some tubular vesicles. There it formed multiple Z rings that could move laterally in both directions along the length of the liposome and coalesce into brighter Z rings. Brighter Z rings produced visible constrictions in the liposome, suggesting that FtsZ itself can assemble the Z ring and generate a force. No other proteins were needed for assembly and force generation. 相似文献
16.
Bacteria are often highly polarized, exhibiting specialized structures at or near the ends of the cell. Among such structures are actin-organizing centers, which mediate the movement of certain pathogenic bacteria within the cytoplasm of an animal host cell; organized arrays of membrane receptors, which govern chemosensory behavior in swimming bacteria; and asymmetrically positioned septa, which generate specialized progeny in differentiating bacteria. This polarization is orchestrated by complex and dynamic changes in the subcellular localization of signal transduction and cytoskeleton proteins as well as of specific regions of the chromosome. Recent work has provided information on how dynamic subcellular localization occurs and how it is exploited by the bacterial cell. The main task of a bacterial cell is to survive and duplicate itself. The bacterium must replicate its genetic material and divide at the correct site in the cell and at the correct time in the cell cycle with high precision. Each kind of bacterium also executes its own strategy to find nutrients in its habitat and to cope with conditions of stress from its environment. This involves moving toward food, adapting to environmental extremes, and, in many cases, entering and exploiting a eukaryotic host. These activities often involve processes that take place at or near the poles of the cell. Here we explore some of the schemes bacteria use to orchestrate dynamic changes at their poles and how these polar events execute cellular functions. In spite of their small size, bacteria have a remarkably complex internal organization and external architecture. Bacterial cells are inherently asymmetric, some more obviously so than others. The most easily recognized asymmetries involve surface structures, e.g., flagella, pili, and stalks that are preferentially assembled at one pole by many bacteria. "New" poles generated at the cell division plane differ from old poles from the previous round of cell division. Even in Escherichia coli, which is generally thought to be symmetrical, old poles are more static than new poles with respect to cell wall assembly (1), and they differ in the deposition of phospholipid domains (2). There are many instances of differential polar functions; among these is the preferential use of old poles when attaching to host cells as in the interaction of Bradyrhizobium with plant root hairs (3) or the polar pili-mediated attachment of the Pseudomonas aeruginosa pathogen to tracheal epithelia (4). An unusual polar organelle that mediates directed motility on solid surfaces is found in the nonpathogenic bacterium Myxococcus xanthus. The gliding motility of this bacterium is propelled by a nozzle-like structure that squirts a polysaccharide-containing slime from the pole of the cell (5). Interestingly, M. xanthus, which has nozzles at both poles, can reverse direction by closing one nozzle and opening the other in response to end-to-end interactions between cells. 相似文献
17.
【目的】分析细菌内源过氧化氢在细胞分裂周期中的时空变化,探讨细菌增殖中过氧化氢的生理功能。【方法】采用组织化学法通过透射电子显微镜技术观察水稻白叶枯病菌内源过氧化氢的积累位置。【结果】不同菌株内源过氧化氢水平不同,在细菌的整个细胞分裂周期中观察到过氧化氢在细胞壁上的积累水平维持稳定,在多个菌株的细胞分裂过程中,除细胞壁之外,还在2个新的位点（类间体结构和核区）出现过氧化氢的大量积累,表现出数量和空间定位的显著变化。【结论】在多个水稻白叶枯病菌菌株中发现胞内额外的大量过氧化氢积累和定位与细胞分裂的进程密切相关,这种过氧化氢的时空变化很可能是细菌分裂时的普遍现象。推测过氧化氢应在细菌增殖中具有重要作用。 相似文献
18.
研究了青霉素、链霉素、氯霉素和螺旋霉素及叶面宝、植物生长素和２，４－Ｄ丁酯激素类物质对稻白叶枯病菌生长的影响。结果表明：３种激素类物质在一定浓度下对白叶枯病菌生长有促进作用。２，４－Ｄ丁酯和植物生长素在浓度低于５μｇ／ｍｌ有明显促进作用，超过５μｇ／ｍｌ时有抑制作用；叶面宝在浓度高于１μｇ／ｍｌ才有促进作用。４种抗菌素对白叶枯病菌均有抑制作用，但其敏感点不同。链霉素和螺旋霉素对白叶枯病菌抑制作用非常敏感，而对其他病原细菌不敏感。抗菌素的反应可作为鉴别白叶枯病菌的有效性状，初步认为激素类物质和抗菌素可用来组配选择性培养基。 相似文献
19.
Fernández MA Albor C Ingelmo-Torres M Nixon SJ Ferguson C Kurzchalia T Tebar F Enrich C Parton RG Pol A 《Science (New York, N.Y.)》2006,313(5793):1628-1632
Liver regeneration is an orchestrated cellular response that coordinates cell activation, lipid metabolism, and cell division. We found that caveolin-1 gene-disrupted mice (cav1-/- mice) exhibited impaired liver regeneration and low survival after a partial hepatectomy. Hepatocytes showed dramatically reduced lipid droplet accumulation and did not advance through the cell division cycle. Treatment of cav1-/- mice with glucose (which is a predominant energy substrate when compared to lipids) drastically increased survival and reestablished progression of the cell cycle. Thus, caveolin-1 plays a crucial role in the mechanisms that coordinate lipid metabolism with the proliferative response occurring in the liver after cellular injury. 相似文献
20.
采用SOS/Umu显色试验研究了2,4K-D丁酯,丁草胺,使它隆,艾割和嗪草酮等5种除草剂的致突变性。结果显示,在SOS/Umu试验中,使它隆和艾割2个受试除草剂可以诱发SOS阳性反应,且呈明显的剂量-效应关系,表明这2种除草剂具有致突变活性。而其它3种除草剂则无诱变效应。 相似文献