Academic literature on the topic 'LptC'
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Journal articles on the topic "LptC"
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Dai, Xiaowei, Min Yuan, Yu Lu, Xiaohong Zhu, Chao Liu, Yifan Zheng, Shuyi Si, Lijie Yuan, Jing Zhang, and Yan Li. "Identification of a Small Molecule That Inhibits the Interaction of LPS Transporters LptA and LptC." Antibiotics 11, no. 10 (October 10, 2022): 1385. http://dx.doi.org/10.3390/antibiotics11101385.
Full textAbstract:
The need for novel antibiotics has become imperative with the increasing prevalence of antibiotic resistance in Gram-negative bacteria in clinics. Acting as a permeability barrier, lipopolysaccharide (LPS) protects Gram-negative bacteria against drugs. LPS is synthesized in cells and transported to the outer membrane (OM) via seven lipopolysaccharide transport (Lpt) proteins (LptA–LptG). Of these seven Lpt proteins, LptC interacts with LptA to transfer LPS from the inner membrane (IM) to the OM, and assembly is aided by LptD/LptE. This interaction among the Lpt proteins is important for the biosynthesis of LPS; therefore, the Lpt proteins, which are significant in the assembly process of LPS, can be a potential target for new antibiotics. In this study, a yeast two-hybrid (Y2H) system was used to screen compounds that could block LPS transport by inhibiting LptA/LptC interaction, which finally disrupts the biosynthesis of the OM. We selected the compound IMB-0042 for this study. Our results suggest that IMB-0042 disrupts LptA/LptC interaction by binding to both LptA and LptC. Escherichia coli cells, when treated with IMB-0042, showed filament morphology, impaired OM integrity, and an accumulation of LPS in the periplasm. IMB-0042 inhibited the growth of Gram-negative bacteria and showed synergistic sensitization to other antibiotics, with low cytotoxicity. Thus, we successfully identified a potential antibacterial agent by using a Y2H system, which blocks the transport of LPS by targeting LptA/LptC interaction in Escherichia coli.
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Sperandeo, Paola, Fion K. Lau, Andrea Carpentieri, Cristina De Castro, Antonio Molinaro, Gianni Dehò, Thomas J. Silhavy, and Alessandra Polissi. "Functional Analysis of the Protein Machinery Required for Transport of Lipopolysaccharide to the Outer Membrane of Escherichia coli." Journal of Bacteriology 190, no. 13 (April 18, 2008): 4460–69. http://dx.doi.org/10.1128/jb.00270-08.
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ABSTRACT Lipopolysaccharide (LPS) is an essential component of the outer membrane (OM) in most gram-negative bacteria, and its structure and biosynthetic pathway are well known. Nevertheless, the mechanisms of transport and assembly of this molecule at the cell surface are poorly understood. The inner membrane (IM) transport protein MsbA is responsible for flipping LPS across the IM. Additional components of the LPS transport machinery downstream of MsbA have been identified, including the OM protein complex LptD/LptE (formerly Imp/RlpB), the periplasmic LptA protein, the IM-associated cytoplasmic ATP binding cassette protein LptB, and LptC (formerly YrbK), an essential IM component of the LPS transport machinery characterized in this work. Here we show that depletion of any of the proteins mentioned above leads to common phenotypes, including (i) the presence of abnormal membrane structures in the periplasm, (ii) accumulation of de novo-synthesized LPS in two membrane fractions with lower density than the OM, and (iii) accumulation of a modified LPS, which is ligated to repeating units of colanic acid in the outer leaflet of the IM. Our results suggest that LptA, LptB, LptC, LptD, and LptE operate in the LPS assembly pathway and, together with other as-yet-unidentified components, could be part of a complex devoted to the transport of LPS from the periplasmic surface of the IM to the OM. Moreover, the location of at least one of these five proteins in every cellular compartment suggests a model for how the LPS assembly pathway is organized and ordered in space.
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Martorana, Alessandra M., Mattia Benedet, Elisa A. Maccagni, Paola Sperandeo, Riccardo Villa, Gianni Dehò, and Alessandra Polissi. "Functional Interaction between the Cytoplasmic ABC Protein LptB and the Inner Membrane LptC Protein, Components of the Lipopolysaccharide Transport Machinery in Escherichia coli." Journal of Bacteriology 198, no. 16 (May 31, 2016): 2192–203. http://dx.doi.org/10.1128/jb.00329-16.
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ABSTRACTThe assembly of lipopolysaccharide (LPS) in the outer leaflet of the outer membrane (OM) requires the transenvelope Lpt (lipopolysaccharide transport) complex, made inEscherichia coliof seven essential proteins located in the inner membrane (IM) (LptBCFG), periplasm (LptA), and OM (LptDE). At the IM, LptBFG constitute an unusual ATP binding cassette (ABC) transporter, composed by the transmembrane LptFG proteins and the cytoplasmic LptB ATPase, which is thought to extract LPS from the IM and to provide the energy for its export across the periplasm to the cell surface. LptC is a small IM bitopic protein that binds to LptBFG and recruits LptA via its N- and C-terminal regions, and its role in LPS export is not completely understood. Here, we show that the expression level oflptBis a critical factor for suppressing lethality of deletions in the C-terminal region of LptC and the functioning of a hybrid Lpt machinery that carriesPa-LptC, the highly divergent LptC orthologue fromPseudomonas aeruginosa. We found that LptB overexpression stabilizes C-terminally truncated LptC mutant proteins, thereby allowing the formation of a sufficient amount of stable IM complexes to support growth. Moreover, the LptB level seems also critical for the assembly of IM complexes carryingPa-LptC which is otherwise defective in interactions with theE. coliLptFG components. Overall, our data suggest that LptB and LptC functionally interact and support a model whereby LptB plays a key role in the assembly of the Lpt machinery.IMPORTANCEThe asymmetric outer membrane (OM) of Gram-negative bacteria contains in its outer leaflet an unusual glycolipid, the lipopolysaccharide (LPS). LPS largely contributes to the peculiar permeability barrier properties of the OM that prevent the entry of many antibiotics, thus making Gram-negative pathogens difficult to treat. InEscherichia colithe LPS transporter (the Lpt machine) is made of seven essential proteins (LptABCDEFG) that form a transenvelope complex. Here, we show that increased expression of the membrane-associated ABC protein LptB can suppress defects of LptC, which participates in the formation of the periplasmic bridge. This reveals functional interactions between these two components and supports a role of LptB in the assembly of the Lpt machine.
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Lin, Yu-Ling, Li-Yi Chen, Chia-Hung Chen, Yen-Ku Liu, Wei-Tung Hsu, Li-Ping Ho, and Kuang-Wen Liao. "A Soybean Oil-Based Liposome-Polymer Transfection Complex as a Codelivery System for DNA and Subunit Vaccines." Journal of Nanomaterials 2012 (2012): 1–12. http://dx.doi.org/10.1155/2012/427306.
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Inexpensive liposome-polymer transfection complexes (LPTCs) were developed and used as for DNA or protein delivery. The particle sizes of the LPTCs were in the range of 212.2 to 312.1 nm, and the zetapotential was +38.7 mV. LPTCs condensed DNA and protected DNA from DNase I digestion and efficiently delivered LPTC/DNA complexes in Balb/3T3 cells. LPTCs also enhanced the cellular uptake of antigen in mouse macrophage cells and stimulated TNF-αrelease in naïve mice splenocytes, both indicating the potential of LPTCs as adjuvants for vaccines.In vivostudies were performed usingH. pylorirelative heat shock protein 60 as an antigen model. The vaccination of BALB/c mice with LPTC-complexed DNA and protein enhanced the humoral immune response. Therefore, we developed a DNA and protein delivery system using LPTCs that is inexpensive, and we successfully applied it to the development of a DNA and subunit vaccine.
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Schultz, Kathryn M., Jimmy B. Feix, and Candice S. Klug. "Disruption of LptA oligomerization and affinity of the LptA-LptC interaction." Protein Science 22, no. 11 (October 21, 2013): 1639–45. http://dx.doi.org/10.1002/pro.2369.
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Hicks, Greg, and Zongchao Jia. "Structural Basis for the Lipopolysaccharide Export Activity of the Bacterial Lipopolysaccharide Transport System." International Journal of Molecular Sciences 19, no. 9 (September 10, 2018): 2680. http://dx.doi.org/10.3390/ijms19092680.
Full textAbstract:
Gram-negative bacteria have a dense outer membrane (OM) coating of lipopolysaccharides, which is essential to their survival. This coating is assembled by the LPS (lipopolysaccharide) transport (Lpt) system, a coordinated seven-subunit protein complex that spans the cellular envelope. LPS transport is driven by an ATPase-dependent mechanism dubbed the “PEZ” model, whereby a continuous stream of LPS molecules is pushed from subunit to subunit. This review explores recent structural and functional findings that have elucidated the subunit-scale mechanisms of LPS transport, including the novel ABC-like mechanism of the LptB2FG subcomplex and the lateral insertion of LPS into the OM by LptD/E. New questions are also raised about the functional significance of LptA oligomerization and LptC. The tightly regulated interactions between these connected subcomplexes suggest a pathway that can react dynamically to membrane stress and may prove to be a valuable target for new antibiotic therapies for Gram-negative pathogens.
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Schultz, Kathryn M., Matthew A. Fischer, Elizabeth L. Noey, and Candice S. Klug. "Disruption of the E. coli LptC dimerization interface and characterization of lipopolysaccharide and LptA binding to monomeric LptC." Protein Science 27, no. 8 (May 9, 2018): 1407–17. http://dx.doi.org/10.1002/pro.3429.
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Heng, Yu, Zheyu Yang, Pengyu Cao, Xi Cheng, and Lei Tao. "Lateral Involvement in Different Sized Papillary Thyroid Carcinomas Patients with Central Lymph Node Metastasis: A Multi-Center Analysis." Journal of Clinical Medicine 11, no. 17 (August 24, 2022): 4975. http://dx.doi.org/10.3390/jcm11174975.
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Objective: To quantitatively predict the probability of lateral lymph node metastasis (LLNM) for papillary thyroid carcinomas (PTC) patients with central lymph node metastasis (CLNM) in order to guide postoperative adjuvant treatment. Methods: Five hundred and three PTC patients with CLNM from three medical centers were retrospectively analyzed. Results: The LLNM rate for all patients was 23.9% (120 in 503), with 15.5% (45 in 291) and 35.4% (75 in 212) for patients with papillary thyroid microcarcinoma (PTMC) and large papillary thyroid carcinoma (LPTC), respectively. Patients with no fewer than five positive central lymph nodes (CLN) exhibited a higher risk of LLNM. For patients with fewer than five positive CLN, a maximum diameter of positive CLN > 0.5 cm and the presence of ipsilateral nodular goiter were identified as independent risk factors of LLNM for papillary thyroid microcarcinoma (PTMC) patients. The independent risk factors of LLNM for large papillary thyroid carcinoma (LPTC) patients included a tumor located in the upper portion of thyroid, maximum tumor diameter ≥ 2.0 cm, maximum diameter of positive CLN > 0.5 cm, and the presence of thyroid capsular invasion. Predictive nomograms were established based on these risk factors for PTMC and LPTC patients, respectively. The accuracy and validity of our newly built models were verified by C-index and calibration curves. PTMC and LPTC patients with fewer than five positive CLN were each stratified into three subgroups based on their nomogram risk scores, and a detailed risk stratification flow chart was established for a more accurate evaluation of LLNM risk in PTC patients. Conclusions: A detailed stratification flow chart for PTC patients with CLNM to quantitatively assess LLNM risk was established, which may aid in clinical decision-making for those patients.
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Xiang, Quanju, Haiyan Wang, Zhongshan Wang, Yizheng Zhang, and Changjiang Dong. "Characterization of lipopolysaccharide transport protein complex." Open Life Sciences 9, no. 2 (February 1, 2014): 131–38. http://dx.doi.org/10.2478/s11535-013-0250-5.
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AbstractLipopolysaccharide (LPS) is an essential component of the outer membranes (OM) of most Gram-negative bacteria, which plays a crucial role in protection of the bacteria from toxic compounds and harsh conditions. The LPS is biosynthesized at the cytoplasmic side of inner membrane (IM), and then transported across the aqueous periplasmic compartment and assembled correctly at the outer membrane. This process is accomplished by seven LPS transport proteins (LptA-G), but the transport mechanism remains poorly understood. Here, we present findings by pull down assays in which the periplasmic component LptA interacts with both the IM complex LptBFGC and the OM complex LptDE in vitro, but not with complex LptBFG. Using purified Lpt proteins, we have successfully reconstituted the seven transport proteins as a complex in vitro. In addition, the LptC may play an essential role in regulating the conformation of LptBFG to secure the lipopolysaccharide from the inner membrane. Our results contribute to the understanding of lipopolysaccharide transport mechanism and will provide a platform to study the detailed mechanism of the LPS transport in vitro.
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Schultz, Kathryn M., and Candice S. Klug. "High-Pressure EPR Spectroscopy Studies of the E. coli Lipopolysaccharide Transport Proteins LptA and LptC." Applied Magnetic Resonance 48, no. 11-12 (September 21, 2017): 1341–53. http://dx.doi.org/10.1007/s00723-017-0948-z.
Full textDissertations / Theses on the topic "LptC"
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VILLA, RICCARDO. "The Lpt multiprotein machinery for LPS transport in Gram-negative bacteria:molecular details of the Lpt interactome." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2012. http://hdl.handle.net/10281/27959.
Full textAbstract:
The hallmark of Gram-negative bacteria is their cell envelope, which is composed of two membranes, the inner or cytoplasmic membrane (IM), and the outer membrane (OM), separated by a compartment (the periplasm) that contains a thin peptidoglycan layer. Lipopolysaccharide (LPS) is the major component of the OM, and it acts as a selective barrier together with the OM proteins (OMPs), preventing the entry of many toxic molecules into the cell. Despite the structure and composition of OM have been elucidated in pivotal studies in the 50s and in the 70s, the factors required for the assembly of this organelle have only recently been identified.
LPS, once it is synthesized in the cytoplasm, has to be translocated through out the cell envelope. Seven essential proteins cooperate in a unique fashion to extract the macromolecule from the IM and deliver it in the outer leaflet of the OM. LptBCFG form the IM complex that empowers the translocation process by ATP hydrolysis (Narita and Tokuda, 2009), LptDE constitute a complex embedded in the OM that finally flips LPS across the OM and deliver it to its final destination (Chng et al., 2010a; Freinkman et al., 2011), and LptA is a periplasmic protein that contacts both the IM and OM complexes (Sperandeo et al. 2007; Tran et al., 2008).
Notably, LptC is single-pass IM protein with a large periplasm-protruding region.
LptC single mutants were obtained in this work by random-mutagenesis, and used in vivo and in vitro experiments to characterize two regions of the protein that distinctly interact with LptA and the IM protein complex LptBFG, respectively.
Chimera versions of LptC, either missing the transmembrane (TM) sequence, or with the IM anchor substituted by a heterologous sequence, were additionally constructed to this purpose.
Moreover, Both LptA and LptC were previously demonstrated to bind LPS in vitro, here it is presented a rapid bioinformatic tool which has been implemented to discover the molecular determinants of LptA for the interaction with Lipid A, the main component of LPS.
Genetic evidences previously obtained in our laboratory together with the presented data strongly support the LPS transport machinery model defined as the trans-envelope complex by Chng and coworkers (Chng et al., 2010a): indeed LptA interacts both with the IM and the OM protein complexes (LptBCFG and LptDE respectively), bridging them together. In support of this model, a phylogeny and structural motif conservation analysis of the Lpt components suggests that the unique structural domain retained in these proteins—despite the low sequence similarity—is the key to make possible the interaction between all the Lpt components.
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Benedet, M. "CHARACTERIZATION OF THE LIPOPOLYSACCHARIDE TRANSPORT MACHINERY USING AN ESCHERICHIA COLI/PSEUDOMONAS AERUGINOSA HYBRID SYSTEMAND ESCHERICHIA COLI LPTC MUTANTS." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/277362.
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Characterization of the lipopolysaccharide transport machinery using an Escherichia coli/Pseudomonas aeruginosa hybrid system and Escherichia coli lptC mutants
The lipopolysaccharide (LPS) transport (Lpt) is an essential process for the biogenesis of the outer membrane (OM) in Gram negative bacteria such as Escherichia coli and Pseudomonas aeruginosa. OM, the first bacterial defense against harsh environment and antimicrobial compounds, is composed by an inner leaflet of phospholipids, an outer leaflet of LPS, and outer membrane proteins.
Lpt system, originally identified in E. coli, is a protein machine responsible for LPS delivery from the inner membrane, where it is synthesized, to the outer membrane. It is composed of seven proteins, LptA through LptG, which form a complex spanning the IM and OM. LptBCFG are located at the IM, LptA in the periplasm, and LptDE at the OM. The lpt genes are evolutionarily conserved and appear to play an essential role in most Proteobacteria.
To understand how LPS is delivered to the OM crossing the hydrophilic periplasmic space, we focused on the role of the periplasmic components LptC and LptA by two main approaches:
i) comparison between E. coli and P. aeruginosa Lpt systems to search for conserved features shared by the Lpt machines of different Gram negative species. By plasmid shuffling technique we showed that P. aeruginosa lptCAB genes can complement E. coli ΔlptCAB mutants, thus indicating that the Pseudomonas proteins can interact with both the other proteins of the Lpt machine and the LPS of E. coli. Although E. coli and P. aeruginosa LptC and LptA proteins exhibit limited sequence identity and similarity, their 3D conformation is conserved. This suggests that LptA and LptC overall structure rather than their amino acid sequence may play a major role in Lpt assembly and LPS recognition and transport;
ii) analysis of E. coli lptC mutants in order to elucidate the role of LptC in the system. E. coli appears to tolerate several mutations in lptC, including deletion of the trans membrane domain; moreover the lethality of the lptC C-terminal region deletion can be suppressed by an appropriate expression of lptB. We thus tested whether E. coli could tolerate the lack of LptC, which was thought to be essential. By plasmid shuffling we obtained viable mutants missing lptC. Genome sequencing of such mutants revealed single amino acid substitutions at the R212 residue of the IM component LptF (lptFSupmutants); in complementation tests, lptFSup mutants suppress lethality of LptC conditional expression mutants. These data show that a specific mutation in LptF can compensate the lack of LptC and suggest that LptC may serve as a chaperon of the Lpt machine assembly and/or activity rather than an essential structural component.
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Bodewits, Karin. "Biosynthesis pathway & transport of endotoxin : promising antibacterial drug targets in the Burkholderia cepacia complex (BCC)." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5791.
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Burkholderia cepacia complex (Bcc) species are opportunistic pathogens in patients with cystic fibrosis (CF), which are able to cause lethal infections. The Bcc are inherently resistant to most classes of antibiotics, which makes successful treatment problematic. Lipid A (also known as endotoxin), the hydrophobic anchor of lipopolysaccaride (LPS), is the bio-active component of LPS. One of several unique characteristics of the lipid A of the Bcc, is the permanent attachment of 4-amino-4-deoxy-L-arabinose (L-Ara4N) to the lipid A molecule. Also, the genes involved in L-Ara4N biosynthesis are necessary for viability in B. cenocepacia. Here we present research on lipid A biosynthesis, modi cation, and transport in the Bcc and highlight promising antimicrobial targets. The synthetic antibiotic CHIR-090 is an inhibitor of LpxC, an enzyme involved in the lipid A biosynthetic pathway. I investigated the activity of CHIR-090 against the Bcc and found that sensitivity to this antibiotic was both species- and strain-specific. CHIR-090 displayed MICs between 0.1 and 12.5 μg/ml against a panel of B. multivorans, the most prevalent Burkholderia species in CF. The species- and strain-specific sensitivity towards CHIR-090 was further explored and a strong correlation was found between the presence of a unique open reading frame, named LpxC2, in resistant species. To address the problem of multiple drug-resistance of the Bcc, we investigated the activity of the pyridoxal 50-phosphate (PLP)-dependent enzyme inhibitor cycloserine (CS) against the Bcc. CS is used as a second line of defense against M. tuberculosis. The activity of the D-enantiomer of CS (DCS) against the Bcc was tested and displayed MICs between 2 and 128 μg/ml and acted bactericidal towards the Bcc. Additionally, DCS inhibition of recombinant ArnB from B. cenocepacia J2315, a PLP-dependent enzyme necessary for viability in the Bcc, was studied. ArnB was inhibited reversibly by DCS. ArnB was further explored as a promising drug-target in the Bcc, but only CS has been identified as an inhibitor so far. In this thesis it was attempted to find the reason why is L-Ara4N modification of lipid A necessary for viability in B. cenocepacia. Therefore, two proteins were characterised, which are involved in lipid A transport: LptA, the periplasmic lipid A binding protein, and LptB, the cytoplasmic ATP-ase. LptA was found to be able to bind both modified and unmodified lipid A in vitro and therefore is not L-Ara4N specific. Furthermore, LptA could bind deep-rough-, rough-, and smooth- LPS, similar to that described for Escherichia coli LptA. The kinetic parameters of LptB were determined in vitro (kcat = 5.71 min-1 and KM = 0.88 mM), and were comparable to E. coli LptB. The ATP-ase activity of LptB was not influenced by the presence of any forms of LPS (modified or non-modified). Therefore, we concluded that both B. cenocepacia J2315 LptA and LptB are not L-Ara4N specific.
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SESTITO, STEFANIA ENZA. "LPS-binding proteins: interaction studies with natural and synthetic ligands." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2015. http://hdl.handle.net/10281/67756.
Full textAbstract:
L’obiettivo di questa tesi è elucidare alcuni aspetti dell’interazione tra proteine che legano il lipopolisaccaride (LPS) batterico e il loro ligando naturale o ligandi di sintesi.
LptC (Lipopolysaccharide transport C) è una proteina batterica che appartiene al sistema di trasporto Lpt, un sistema di 7 proteine essenziali che trasportano l’LPS sulla membrana esterna dei batteri Gram negativi dopo la sua biosintesi. Sebbene molti elementi della biosintesi dell’LPS siano stati elucidati, il preciso meccanismo di trasporto è ancora poco chiaro. Poiché LptC può essere considerata come proteina modello del sistema Lpt, in quanto presenta lo stesso folding delle altre proteine ed è la prima ad essere localizzata nel periplasma, abbiamo sviluppato ed ottimizzato un saggio di binding in vitro per studiare la sua interazione con l’LPS. Abbiamo ottenuto, per la prima volta, dettagliate informazioni sui parametri termodinamici e cinetici dell’interazione LptC-LPS. Abbiamo infatti dimostrato che in vitro il binding LptC-LPS è irreversibile con una Kd dell’ordine del μM. Considerando le analogie strutturali tra LptC e la proteina eucariotica CD14, appartenente al sistema recettoriale del TLR4, in modo analogo è stata studiata l’interazione di LptC con la molecola sintetica IAXO-102, un noto ligando di CD14. È emerso che IAXO-102 condivide lo stesso sito di legame dell’LPS e che l’interazione con la proteina è irreversibile con un’affinità inferiore a quella LptC-LPS. IAXO-102 può dunque essere considerato un prototipo per lo sviluppo di una nuova generazione di antibiotici che ha come target la biogenesi dell’LPS.
L’LPS è in grado di interagire con molte altre proteine, tra le quali quelle del sistema dell’immunità innata (TLR4, CD14, MD-2). Il riconoscimento dell’LPS da parte di questi recettori induce una forte risposta infiammatoria che termina con la produzione di citochine pro-infiammatorie e fattori immunomodulatori. Questa reazione infiammatoria è utile all’organismo, ma quando si manifesta in modo eccessivamente potente e sregolato induce sepsi, processi infiammatori e sindromi autoimmuni per le quali non è ancora disponibile un trattamento farmacologico. Una possibile soluzione al problema consiste nella ricerca e nello sviluppo di composti in grado di modulare questa eccessiva attivazione. Nella seconda parte di questo lavoro, sono riportate le caratterizzazioni biologiche di alcuni composti di sintesi con caratteristiche chimiche differenti. Di tutti i composti è stata valutata la tossicità mediante saggio dell’MTT e l’attività modulatoria del pathway del TLR4 utilizzando cellule HEK stabilmente trasfettate con i geni del TLR4, CD14 ed MD-2. Ulteriori caratterizzazioni sono state effettuate sui composti più promettenti, effettuando saggi in vitro su cellule HEK trasfettate con il complesso umano o murino TLR4•MD-2 e saggi in vivo. Infine, abbiamo investigato la possibile correlazione tra le note proprietà anti-infiammatorie di alcuni composti naturali, come i composti fenolici presenti nell’olio di oliva, e il pathway del TLR4. L’obiettivo di questo lavoro è duplice: individuare un lead compound come possibile modulatore del TLR4, ma anche discriminare quali caratteristiche chimiche siano importanti per ottenere questo effetto. Inoltre, le informazioni ottenute potrebbero essere estremamente utili per guidare il rational design di altri modulatori del TLR4.The purpose of this work is the elucidation of some aspects of the interaction between lipopolysaccharide (LPS) binding proteins and their natural ligand or synthetic compounds. LptC (Lipopolysaccharide transport C) is a bacterial protein belonging to Lpt complex, a molecular machinery composed of 7 essential proteins involved in the transport of LPS to the outer membrane in Gram negative bacteria after its biogenesis. Although many elements of LPS biosynthesis have been clarified, the precise mechanism of transport is still not completely understood. Since LptC can be considered as a model protein of Lpt complex, sharing the same folding of other proteins and being the first one in the periplasm, we have developed and optimized an in vitro binding assay to study its interaction with LPS. We have obtained, for the first time, detailed information about the thermodynamic and kinetic parameters of LptC-LPS binding. We have shown that the in vitro LptC-LPS binding is irreversible with a Kd of the order of μM. Considering the structural similarities between LptC and the eukaryotic protein CD14, belonging to TLR4 receptor system, the binding between LptC and the synthetic molecule iaxo-102, a known ligand of CD14, has been investigated. It is evident that iaxo-102 shares the same binding site of LPS and that the binding is irreversible with an affinity lower than that LptC-LPS. So, iaxo-102 can be considered as a lead compound for the development a new generation of antibiotics targeting the biogenesis of LPS. LPS also binds to other proteins, such as those of innate immunity TLR4, CD14 and MD-2. The LPS recognition by these receptors induces the production of pro-inflammatory cytokines and immunomodulators that trigger the inflammatory and immune responses. These reactions are useful for the organism, but when TLR4 activation is too strong or not well regulated induces sepsis, inflammation and autoimmune syndromes, which still lack a pharmacological treatment. A possible solution to solve this problem consists in the research and development of compounds which modulate this excessive activation. In the second part of thesis work, the biological characterization of some synthetic compounds, with different chemical features, have been reported. All compounds have been screened for their toxicity using MTT assay, and their modulatory activity on TLR4 pathway by using HEK cells stably transfected with TLR4, CD14 and MD-2 genes. The best compounds have been further characterized by in vitro assays on HEK cells transfected with the human or murine complex TLR4·MD-2 and in vivo studies. Finally, the possible correlation between the known anti-inflammatory properties of some natural compounds, such as the phenolic compounds of olive oil, and TLR4 activity has been investigated. The aim of this study is double: to find a lead compound active on TLR4 pathway, but also to discriminate which chemical features are important to obtain this effect. In addition, the information obtained could be very useful to guide the rational design of other TLR4 modulators.
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CIARAMELLI, CARLOTTA. "Synthesis and characterization of new small-molecule ligands of LPS binding proteins." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2015. http://hdl.handle.net/10281/77016.
Full textAbstract:
Lo scopo del presente lavoro è la progettazione, la sintesi e la caratterizzazione di nuove small molecules, attive come ligandi di LPS (lipopolisaccaridi)-binding proteins. Gli LPS, o endotossine batteriche, sono macromolecole anfifiliche ubiquitarie sulla membrana esterna dei batteri Gram-negativi. Le proteine che legano gli LPS studiate nel corso di questo progetto di tesi di dottorato appartengono a due categorie: le proteine batteriche di trasporto Lpt e il sistema recettoriale TLR4, che comprende anche i co-recettori LBP, CD14, MD2.
Le proteine Lpt, e in particolare la proteina LptC, sono responsabili del meccanismo di esportazione del LPS alla superficie cellulare, che è uno step fondamentale della via biosintetica dell’LPS. Pertanto, la biogenesi dell’LPS rappresenta un target ideale per lo sviluppo di nuovi antibiotici contro i batteri Gram-negativi. Inoltre, le strutture delle proteine Lpt sono state risolte, ma il meccanismo di trasporto è ancora da elucidare.
Nel presente lavoro di tesi sono stati utilizzate diverse tecniche per studiare l'interazione tra LPS e LptC, con particolare attenzione agli studi di interazione via NMR. Inoltre, un nuovo LPS fluorescente è stato prodotto ed è stato utilizzato come tool per studi di interazione LPS-LptC con tecniche di fluorescenza. Sono state anche sviluppate alcune nuove molecole sintetiche. Questi glicolipidi sono stati progettati e sintetizzati per ottenere ligandi di LptC e, in prospettiva, potenziali antibiotici contro i batteri Gram-negativi.
Il Toll-like receptor 4 (TLR4), il recettore dell'immunità innata, riconosce l’LPS aiutato da altre proteine (LBP, CD14 e MD-2) ed è responsabile dell'induzione della risposta infiammatoria. Molecole sintetiche in grado di modulare l'attività dei recettori dell’immunità innata sono un potente mezzo per studiare il sistema recettoriale TLR4 e hanno grande interesse farmacologico come adiuvanti vaccinali (agonisti), agenti antisepsi e anti-infiammatori (antagonisti).
L’attività biologica di glicolipidi con una funzione amminica (IAXO-102) come antagonisti del TLR4 è stata chiaramente dimostrata dal nostro gruppo di ricerca. La sintesi di molecole derivate da IAXO-102, che mantengano l'attività biologica del precursore, è stato un obiettivo di questo lavoro. In particolare, sono state portate a termine le sintesi di sonde fluorescenti, utilizzate per studi di interazione, derivati zwitterionici e molecole dimeriche. Nei nostri laboratori sono stati ottenuti anche antagonisti anionici del TLR4 con una struttura chimica più simile a Lipide A. Lo scopo di questo lavoro è stato valutare, tramite esperimenti NMR, la loro capacità di legare co-recettore dell'immunità innata MD-2.
Il carattere anfifilico degli analoghi sintetici del lipide A sintetizzati finora è spesso associato ad una bassa solubilità in acqua e a scarsa biodisponibilità. Invece, i composti attivi sul TLR4 di origine naturale hanno una migliore solubilità e biodisponibilità. La modifica chimica di queste strutture è molto utile per modulare l'attività biologica e per migliorare la specificità nei confronti del target. Di conseguenza, in una fase successiva di questo lavoro di tesi, è stata intrapresa la sintesi di nuove molecole con strutture chimiche ispirate ai modulatori naturali del TLR4. Recentemente è stato dimostrato che alcuni composti fenolici estratti da olio di oliva hanno una buona attività come antagonisti del TLR4. Pertanto, la sintesi di alcuni analoghi di queste molecole è stata eseguita per ottenere nuovi potenziali antagonisti del TLR4, con una migliore solubilità in acqua e una ridotta tossicità.The purpose of this work is the design, synthesis and characterization of new small molecules, active as ligands of two different lipopolysaccharide (LPS)-binding proteins. LPS, or bacterial endotoxin, is an amphiphilic macromolecule ubiquitous on the outer membrane of Gram-negative bacteria. The LPS binding proteins studied during this thesis project belong to two classes: the bacterial proteins of the Lpt transport machinery and the mammalian TLR4 receptor system, including the co-receptors LBP, CD14, MD-2. Lpt proteins, and in particular the protein LptC, are responsible for the export mechanism of LPS to the cell surface of Gram negative bacteria, which is a fundamental step of the LPS biosynthetic pathway. Therefore, the LPS biogenesis represents an ideal target for development of novel antibiotics against Gram-negative bacteria. Moreover, the structures of Lpt proteins have been elucidated, but very little is known about the mechanism of LPS transport. In this thesis work different techniques were used to study the interaction between LPS and LptC, particularly NMR binding studies. Moreover, a new fluorescent LPS was produced and it was used as a tool to perform LPS-LptC interaction studies with fluorescence techniques. Some new synthetic molecules were also developed during this thesis. Glycolipidic small molecules were designed and synthesized in order to obtain LptC ligands and, in perspective, potential antibiotics against Gram-negative bacteria. Toll-like receptor 4 (TLR4), the innate immunity receptor, recognizes LPS, helped by other proteins (LBP, CD14 and MD-2), and it is responsible for the induction of inflammatory responses. Synthetic small molecules able to modulate innate immunity receptors activity are a powerful mean to study the TLR4 receptor system and have great pharmacological interest as vaccine adjuvants (agonists), antisepsis and anti-inflammatory agents (antagonists). Antagonist activity on TLR4 receptor system of amino glycolipids (IAXO-102) was clearly demonstrated by our research group. The synthesis of molecules derived from IAXO-102 which retain the biological activity of the precursor was a target of this work. In particular, the synthesis of fluorescent probes, used for binding studies, zwitterionic derivatives and dimeric molecules were performed. Anionic TLR4 antagonists with a chemical structure more similar to Lipid A were also obtained in our labs. The aim of this work was the evaluation via NMR binding experiments of their ability to bind the innate immunity co-receptor MD-2. The amphiphilic character of the synthetic lipid A analogues synthesized so far is often associated with low water solubility and poor bioavailability. In this respect, the natural TLR4-active compounds have better solubility and bioavailability. The chemical modification of these structures is very helpful to modulate their biological activity and to enhance target specificity. Consequently, in a later stage of this work, the synthesis of new small molecules with chemical structures inspired to natural TLR4 modulators was pursued. Very recently it was found that some phenolic compounds from olive oil extracts presented a good activity as TLR4 antagonists. The synthesis of some analogues of these molecules was performed to obtain new potential TLR4 antagonists with better water solubility and reduced toxicity.
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Garner, Ronald Aaron. "Oxidative Assembly of the Outer Membrane Lipopolysaccharide Translocon LptD/E and Progress towards Its X-Ray Crystal Structure." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13064991.
Full textAbstract:
Lipopolysaccharide (LPS) is the glycolipid that comprises the outer leaflet of the Gram-negative outer membrane (OM). Because it is essential in nearly all Gram-negative species, and because it is responsible for making these bacteria impervious to many types of antibiotics, LPS biogenesis has become an important area of research. While its biosynthesis at the cytoplasmic face of the inner membrane (IM) is well studied, the process by which it is removed from the IM, transported across the aqueous periplasmic compartment, and specifically inserted into the outer leaflet of the OM is only beginning to be understood. This transport process is mediated by the essential seven-protein LPS transport (Lpt) complex, LptA/B/C/D/E/F/G. The OM portion of the exporter, LptD/E, is a unique plug-and-barrel protein complex in which LptE, a lipoprotein, sits inside of LptD, a β-barrel integral membrane protein. LptD is of particular interest, as it is the target of an antibiotic in Pseudomonas aeruginosa.
Part I of this thesis investigates how the cell forms the two non-consecutive disulfide bonds that connect LptD's C-terminal β-barrel to its N-terminal soluble domain. These disulfides, one of which is almost universally conserved among Gram-negatives, are essential for cell viability. Here, we show that an intermediate oxidation state with non-native disulfide bonds accumulates in the absence of LptE and in strains defective in either LptE or LptD. We then demonstrate that this observed intermediate is on-pathway and part of the native LptD oxidative folding pathway. Using a defective mutant of DsbA, the protein that introduces disulfide bonds into LptD, we are able to identify additional intermediates in the LptD oxidative folding pathway. We ultimately demonstrate that the disulfide rearrangement that activates the LptD/E complex occurs following an exceptionally slow β-barrel assembly step and is dependent on the presence of LptE.
Part II describes work towards obtaining X-ray crystal structures of the LptD N-terminal domain and LptD/E complex. Expression construct and purification optimization enabled the production of stable LptD/E in quantities that make crystallography feasible. Numerous precipitants, detergents, and additives were screened, ultimately resulting in protein crystals that diffract to a resolution of 3.85 Å.Chemistry and Chemical Biology
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Xue, Mingyu. "Identification and Characterization of Intermediates during Folding on the β-Barrel Assembly Machine in Escherichia coli." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11594.
Full textAbstract:
β-barrel membrane proteins play important structural and functional roles in Gram negative bacteria and in mitochondria and chloroplasts of eukaryotes. A conserved machine is responsible for the folding and insertion of β-barrel membrane proteins but its mechanism remains largely
unknown. In E. coli, a five protein β-barrel assembly machine (Bam) assembles β-barrel proteins into the outer membrane (OM). Among all β-barrel membrane proteins in E. coli
, the β-barrel component of the OM LPS translocon is one of
only two essential β-barrels, the other being the
central component of the Bam machinery itself. The OM LPS translocon, which consists of OM β-barrel protein LptD (lipopolysaccharide transport) and OM lipoprotein LptE, is responsible for the final export of LPS molecules into the outer leaflet of the OM, resulting in an asymmetric bilayer that blocks the entry of toxic molecules such as antibiotics. This thesis describes the characterization of the biogenesis pathway of the OM LPS translocon and its folding and insertion
into the OM by the Bam machinery.
An in vivo S35-Methionine pulse-labeling assay was developed to identify intermediates along the biogenesis of the OM LPS translocon. Seven intermediates were identified along the
pathway. We show that proper assembly of the OM LPS translocon involves an oxidative disulfide bond rearrangement from a nonfunctional intermediate containing non-native disulfides. We also found that the rate determining step of OM LPS translocon biogenesis is β-barrels folding process by the Bam machinery.
Using in vivo chemical crosslinking, we accumulated and trapped a mutant form of LptD on BamA, the central component of the Bam machinery. We extended the S35-Methionine pulse-labeling method to allow chemical crosslinking of substrates on the Bam complex and trapped LptD while it was being folded on the Bam machine. We demonstrated that the interaction between LptD and BamA is independent of LptE, while that between LptD and BamD, the other
essential component of the Bam complex beside BamA, is LptE dependent. Based on these findings, we proposed a model of Bam-assisted folding of the OM LPS translocon in which LptE
templates the folding of LptD.Chemistry and Chemical Biology
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Pandey, Sundar. "Novel Role of Pseudomonas Aeruginosa LptD Operon." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3734.
Full textAbstract:
Pseudomonas aeruginosais an opportunistic pathogen that infects cystic fibrosis (CF) patients contributing to their high morbidity and mortality. P. aeruginosaundergoes a phenotypic conversion in the CF lung, from nonmucoid to mucoid, by constitutively producing a polysaccharide called alginate. These mucoid strains often revert to nonmucoid in vitrodue to second-site suppressor mutations. We hypothesized that mapping these mutations would lead to the identification of novel genes involved in alginate production. In a previous study, a mucoid strain, PDO300 (PAOmucA22), was used to isolate suppressors of alginate phenotype (sap). One of the uncharacterized nonmucoid revertants, sap27, is the subject of this study. The mucoid phenotype in sap27was restored by pMO012217 from a minimal tiling path cosmid library. The cosmid pMO012217 harbors 18 P. aeruginosaopen reading frames (ORF). The cosmid was mutagenized with a transposon to map the contributing gene. It was mapped tolptD(PA0595) encoding lipopolysaccharide transport protein. E. coliLptD transports lipopolysaccharide to the outer leaflet of the outer membrane. The Alg+phenotype was restored upon complementation with P. aeruginosa lptDalone, suggesting that sap27likely harbor a chromosomal mutation inlptD. Sequencing analysis of sap27showed the presence of a mutation not in lptDbut in algO, which encodes a periplasmic protease protein. This suggests LptD is able to bypass analgO mutation by positively regulating alginate production. The lptD is a part of a three-gene operon lptD-surA-pdxA. SurA is an essential protein for survival in starvation and a major chaperone protein for all outer membrane proteins and PdxA is a NAD-dependent dehydrogenase and is involved in the vitamin B6biosynthetic pathway. Pyridoxal 5’-phosphate (PLP) is the active form of vitamin B6.P. aeruginosagrown in a media supplemented with PLP increased production of pyocyanin, a virulence factor. The PLP and aromatic amino acids are synthesized from a common precursor chorismic acid. We demonstrated an increase in pyocyanin production when the bacteria were cultured supplemented by the aromatic amino acids phenylalanine. We concluded that the lptDoperon plays a role in the P. aeruginosavirulence by regulating alginate and pyocyanin production.
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Martins, José Antônio. "Vocoder LPC com quantização vetorial." [s.n.], 1991. http://repositorio.unicamp.br/jspui/handle/REPOSIP/261389.
Full textAbstract:
Orientador : Fabio ViolaroDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia Eletrica
Made available in DSpace on 2018-07-13T23:59:40Z (GMT). No. of bitstreams: 1 Martins_JoseAntonio_M.pdf: 6784204 bytes, checksum: 4e9df50ca8f72e1710d541924b76a67c (MD5) Previous issue date: 1991
Resumo: Neste trabalho são descritos os princípios do vocoder LPC, sendo mostrados os métodos para cálculo dos parâmetros do mesmo. Também são apresentados os resultados de simulações de vocoders LPC usando quantização escalar, quantização vetorial e interpolação dos parâmetros quantizados. Inicialmente foi projetado um vocoder LPC não quantizado, o qual serviu de padrão para a avaliação dos vocoders quantizados. Usando a quantização escalar dos coeficientes razão log-área foi obtido um vocoder à taxa de 2200 bit /s, assegurando uma boa qualidade e alta inteligibilidade da voz sintetizada. Com o uso da quantização vetorial obteve-se um bom desempenho em taxas da ordem de 1000 bit/s. Essas taxas foram reduzidas em 50% com o uso da interpolação linear, transmitindo apenas os parâmetros dos quadros ímpares. Assim, conseguiu-se vocoders com taxas ao redor de 500 bit/s, apresentando voz sintetizada com degradação em relação aos sistemas anteriores, mas ainda assegurando uma boa inteligibilidade
Abstract: Not informed.
Mestrado
Eletronica e Comunicações
Mestre em Engenharia Elétrica
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Titecat, Marie. "Evaluation d’une nouvelle classe d’antibiotiques : les inhibiteurs de LpxC." Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S038.
Full textAbstract:
L’émergence et la diffusion de la résistance aux antibiotiques au sein des bactéries à Gram négatif (BGN) sont aujourd’hui des enjeux de Santé Publique nationaux et internationaux. La multi-résistance aux antibiotiques concerne non seulement des espèces fréquemment responsables d’infections nosocomiales mais aussi des espèces hautement virulentes comme Yersinia pestis, agent de la peste et du bioterrorisme. Dans ce contexte, la mise au point de nouvelles molécules actives sur d’autres cibles bactériennes est primordiale. La métallo-enzyme LpxC catalyse la première étape irréversible de la biosynthèse du lipide A, constituant majeur de la membrane externe des bactéries à Gram négatif. Des inhibiteurs de LpxC sont ainsi développés depuis une vingtaine d’années mais leur spectre sur les BGN était initialement limité aux entérobactéries et leur activité partielle sur P. aeruginosa. Dans ce travail nous avons participé à l’optimisation de la structure chimique de ces molécules grâce à une approche dynamique des interactions enzymes/inhibiteurs utilisant la résonance magnétique nucléaire (RMN). Cette technique a permis l’élaboration d’un nouvel inhibiteur de LpxC, le LPC-058, caractérisé par une forte affinité pour l’enzyme (Ki = 3,5 ± 0,2 pM). Nous avons évalué in vitro l’activité antibiotique du LPC-058 et de trois autres composés (CHIR-090, LPC-011 et LPC-087) vis-à-vis de 369 souches cliniques responsables d’infections nosocomiales aux profils de résistance variés. Le LPC-058 présentait le plus large spectre d’activité en particulier sur A. baumannii et les valeurs de CMI les plus basses (CMI90 = 0,12 mg/L pour les entérobactéries et 0,5 mg/L pour P. aeruginosa). Il était bactéricide vis-à-vis de souches multi-résistantes et son action était synergique avec les C3G, l’imipénème, l’amikacine et la ciprofloxacine vis-à-vis de souches de K. pneumoniae, P. aeruginosa et A. baumannii productrice de carbapénémases, respectivement KPC-2, VIM-1 et OXA-23. Le LPC-058 présentait néanmoins une forte fixation protéique et, in vivo, son volume de distribution était limité au compartiment sanguin (Vd = 1,1 L/kg). Nous avons évalué son activité in vivo dans un modèle murin de peste bubonique car il s’agit de l’une des infections les plus virulentes pour l’homme. Nous avons obtenu une survie de 87 % après 5 jours de traitement à la posologie de 10 mg/kg q8h par voie veineuse. Le LPC-058 occasionnant des diarrhées chez le rongeur, nous avons évalué un de ses dérivés, le LPC-B, caractérisé par une moindre fixation protéique, un plus grand volume de distribution et l’absence d’effets secondaires chez la souris, même à fortes doses. Nous avons démontré qu’à la posologie de 200 mg/kg par voie veineuse, cet antibiotique était aussi efficace que la doxycycline (traitement de référence de la peste). L’ensemble de ces travaux souligne le rôle potentiel des inhibiteurs de LpxC dans la prise en charge des infections par des bactéries multi-résistantes ou hautement virulentesAntimicrobial resistance among Gram-negative bacteria (GNB) has become a national and international public health concern. Resistant strains are involved in nosocomial diseases and in highly virulent infections, such as plague caused by Yersinia pestis, a potential biological terrorism agent. In this context the development of new antimicrobial compounds efficient on new bacterial targets is critical. LpxC metallo-enzyme catalyzes the first commitment step of the lipid A biosynthesis, a major component of the Gram negative cell wall. LpxC inhibitors have been developed for twenty years but their activity was restricted to enterobacteria and weak against Pseudomonas aeruginosa. In this study, we have collaborated in the chemical optimization of the compounds thanks to a dynamic approach of enzyme/inhibitor interactions brought by nuclear magnetic resonance (NMR). This technology enabled the development of LPC-058, a new inhibitor, showing a high potency against LpxC (Ki = 3.5 ± 0.2 pM). We studied the in vitro efficacy of LPC-058 and three other compounds (CHIR-090, LPC-011 and LPC-087) against 369 clinical strains responsible for nosocomial infections with various antibiotic resistance profiles. In this part, LPC-058 displayed the broadest spectrum of efficacy, even on Acinetobacter baumannii with the lowest MIC values (MIC90 = 0.12 mg/L against enterobacteria and 0.5 mg/L against P. aeruginosa). It showed bactericidal activity against multi-resistant strains and synergistic activity in association with third generation cephalosporins, imipenem, amikacin and ciprofloxacin against carbapenemase producing Klebsiella pneumoniae, P. aeruginosa et A. baumannii strains (respectively KPC-2, VIM-1 and OXA-23). However, LPC-058 was constrained by strong protein interactions and a small volume of distribution (Vd = 1.1 L/kg). In vivo efficacy was studied in a murine model of bubonic plague. A 87% survival rate was obtained after five days of 10 mg/kg q8h intravenous administration. As LPC-058 treatment was associated to diarrheas in mice, we evaluated another derivate, LPC-B, characterized by a larger volume of distribution, minor protein fixation and less side effects, even for a high dose posology. We demonstrated a comparable efficacy between 200 mg/kg LPC-B treatment and doxycyclin administration (recommended in plague treatment). This work highlights the potential use of LpxC inhibitors in the management of infections caused by multi-resistant or highly virulent Gram-negative bacteria
Books on the topic "LptC"
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LPIC I. Indianapolis, Ind: Que, 2005.
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Vazquez, Antonio. Practical LPIC-3 300. Berkeley, CA: Apress, 2019. http://dx.doi.org/10.1007/978-1-4842-4473-9.
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LPIC-1 in depth. Boston, MA: Course Technology/Cengage Learning, 2010.
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Polding, Liz. LPC skills online. Oxford: Oxford Institute of Legal Practice, 2010.
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Jill, Cripps, ed. LPC skills online. Oxford: Oxford Institute of Legal Practice, 2010.
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Commitee, London Planning Advisory. Introducing LPAC: Planning for Greater London. London: LPAC, 1998.
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Imogen, Clout, and Miles George, eds. Foundations for the LPC. 2nd ed. London: Blackstone Press, 1998.
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Miles, George, and Pauline Denyer. Foundations for the LPC. Oxford: Oxford University Press, 2011.
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LPIC-1/CompTIA Linux+ certification all-in-one exam guide (exams LPIC-1/LX0-101 & LX0-102). New York: McGraw-Hill, 2012.
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Clinton, David. Practical LPIC-1 Linux Certification Study Guide. Berkeley, CA: Apress, 2016. http://dx.doi.org/10.1007/978-1-4842-2358-1.
Full textBook chapters on the topic "LptC"
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El-Baba, Mazen. "Lateral Prefrontal Cortex (LPFC)." In Encyclopedia of Personality and Individual Differences, 2581–84. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-319-24612-3_772.
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El-Baba, Mazen. "Lateral Prefrontal Cortex (LPFC)." In Encyclopedia of Personality and Individual Differences, 1–4. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-28099-8_772-1.
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Miyazaki, Ryoji, Hiroyuki Mori, and Yoshinori Akiyama. "A Photo-Crosslinking Approach to Monitoring the Assembly of an LptD Intermediate with LptE in a Living Cell." In Lipopolysaccharide Transport, 97–107. New York, NY: Springer US, 2022. http://dx.doi.org/10.1007/978-1-0716-2581-1_7.
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Floreani, Annarosa, and Christophe Corpechot. "Low Phospholipid-Associated Cholelithiasis (LPAC)." In Diseases of the Liver and Biliary Tree, 115–20. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65908-0_7.
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Vazquez, Antonio. "Starting with OpenLDAP." In Practical LPIC-3 300, 3–32. Berkeley, CA: Apress, 2019. http://dx.doi.org/10.1007/978-1-4842-4473-9_1.
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Vazquez, Antonio. "File Services in Samba." In Practical LPIC-3 300, 257–91. Berkeley, CA: Apress, 2019. http://dx.doi.org/10.1007/978-1-4842-4473-9_10.
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Vazquez, Antonio. "Linux File System and Share and Service Permissions." In Practical LPIC-3 300, 293–315. Berkeley, CA: Apress, 2019. http://dx.doi.org/10.1007/978-1-4842-4473-9_11.
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Vazquez, Antonio. "Print Services." In Practical LPIC-3 300, 317–63. Berkeley, CA: Apress, 2019. http://dx.doi.org/10.1007/978-1-4842-4473-9_12.
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Vazquez, Antonio. "Managing User Accounts and Groups." In Practical LPIC-3 300, 365–79. Berkeley, CA: Apress, 2019. http://dx.doi.org/10.1007/978-1-4842-4473-9_13.
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Vazquez, Antonio. "Authentication, Authorization, and Winbind." In Practical LPIC-3 300, 381–94. Berkeley, CA: Apress, 2019. http://dx.doi.org/10.1007/978-1-4842-4473-9_14.
Full textConference papers on the topic "LptC"
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Wang, Hongxin, Jigen Peng, and Shigang Yue. "An improved LPTC neural model for background motion direction estimation." In 2017 Joint IEEE International Conference on Development and Learning and Epigenetic Robotics (ICDL-EpiRob). IEEE, 2017. http://dx.doi.org/10.1109/devlrn.2017.8329786.
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Gupta, Harshita, and Divya Gupta. "LPC and LPCC method of feature extraction in Speech Recognition System." In 2016 6th International Conference - Cloud System and Big Data Engineering (Confluence). IEEE, 2016. http://dx.doi.org/10.1109/confluence.2016.7508171.
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Godino-Llorente, Juan I., Santiago Aguilera-Navarro, and Pedro Gómez-Vilda. "LPC, LPCC and MFCC parameterisation applied to the detection of voice impairments." In 6th International Conference on Spoken Language Processing (ICSLP 2000). ISCA: ISCA, 2000. http://dx.doi.org/10.21437/icslp.2000-695.
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Naung, Shine Win, Mohammad Rahmati, and Hamed Farokhi. "Numerical Investigation of the Effect of Flutter Instability of the Blade on the Unsteady Flow in a Modern Low-Pressure Turbine." In ASME Turbo Expo 2020: Turbomachinery Technical Conference and Exposition. American Society of Mechanical Engineers, 2020. http://dx.doi.org/10.1115/gt2020-15959.
Full textAbstract:
Abstract Modern aeronautical Low-Pressure Turbines (LPTs) are prone to aeroelastic instability problems such as flutter. The aerodynamic performance of a modern LPT is often influenced by the interaction between the transient flow and the dynamic behaviour of the blade. Therefore, the investigation and understanding of the physics behind the interaction between the unsteady flow and the flutter phenomenon of the blade in an LPT, which is normally left out by existing studies, is an important aspect of the research to improve the aerodynamic performance of the turbine as well as to ensure the blade mechanical integrity. In this paper, a novel analysis is conducted to explore the flutter instability in a modern LPT, T106A turbine, using two inter blade phase angles (IBPAs), and their effects on the unsteady flow field are investigated. The zero degree and 180 degrees IBPAs are considered in this paper. A high-fidelity direct numerical simulation method is used for the flow simulations. Another distinctive feature of this paper is the use of the 3D model to analyse the effects associated with the 3D blade structure and the 3D vibration mode. The investigation and identification of adequate working ranges of the harmonic balance method, which has been widely used for the aeromechanical analysis of turbomachines, are also presented in this work. This paper will bridge a key gap in the knowledge of aeroelasticity modelling and analysis of modern LPTs.
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Bolinches-Gisbert, Marc, David Cadrecha, Roque Corral, and Fernando Gisbert. "Numerical and Experimental Investigation of the Reynolds Number and Reduced Frequency Effects on Low-Pressure Turbine Airfoils." In ASME Turbo Expo 2020: Turbomachinery Technical Conference and Exposition. American Society of Mechanical Engineers, 2020. http://dx.doi.org/10.1115/gt2020-14224.
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Abstract This paper compares experimental and numerical data for a low-speed high-lift Low Pressure Turbine (LPT) cascade under unsteady flow conditions. Three Reynolds numbers representative of LPTs have been tested, namely, 5 × 104, 105, 2 × 105; at two reduced frequencies, fr = 0.5 and 1, also representative of LPTs. The experimental data was obtained at the low-speed linear cascade wind-tunnel at the Polytechnic University of Madrid using hot-wire, LDV and pressure tappings. The numerical solver employs a sixth order compact scheme based on the Flux Reconstruction method for spatial discretization and a fourth order Runge-Kutta method to march in time. The longest case ran 550 hours on 40 GPUs to reach a statistically periodic state. Pressure coefficients around the profile, boundary layer profiles and exit cross-section distributions of velocity, pressure loss defect, shear Reynolds stress and angle are compared against high-quality experimental data. Cascade loss and exit angle have also been compared against experimental data. Very good agreement between experimental and numerical data is seen. The results demonstrate the suitability of the present methodology to predict the aerodynamic properties unsteady flows around LPT linear cascades accurately.
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Qian, Yingjin, Xi Li, Shuichi Ihara, Andreas Dilger, Carlos Thomaz, Shilong Wang, Wen Cheng, et al. "LPCC." In SC '19: The International Conference for High Performance Computing, Networking, Storage, and Analysis. New York, NY, USA: ACM, 2019. http://dx.doi.org/10.1145/3295500.3356139.
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Serrano González, Adolfo, and José Ramón Fernández Aparicio. "Turbine Tone Noise Prediction Using a Linearized CFD Solver: Comparison With Measurements." In ASME Turbo Expo 2015: Turbine Technical Conference and Exposition. American Society of Mechanical Engineers, 2015. http://dx.doi.org/10.1115/gt2015-42410.
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The capability of a Linearized CFD Method for predicting turbine tone noise is investigated through comparison with measurements. To start with, a benchmark problem on flat plates is presented, and results are put together with those published by other authors. Then, numerical predictions are compared with measurements from two Low Pressure Turbines (LPTs), which have been tested in different facilities. The first specimen is a three stage cold flow rig, noise tested in the CTA facility (Bilbao, Spain) in 2012, and funded by the Clean Sky EU Program. The second is the ANTLE LPT rig, full scale, cold flow, noise tested in the TSTF in Rolls-Royce (Derby, United Kingdom) in 2005 and funded by the SILENCE(R) EU Funded Program. The comparison includes multi-stage effects, clocking sensitivities and acoustic scattering through Outlet Guide Vanes (OGVs).
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Bertini, Francesco, Martina Credi, Michele Marconcini, and Matteo Giovannini. "A Path Towards the Aerodynamic Robust Design of Low Pressure Turbines." In ASME Turbo Expo 2012: Turbine Technical Conference and Exposition. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/gt2012-69456.
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Airline companies are continuously demanding lower-fuel-consuming engines and this leads to investigating innovative configurations and to further improving single module performance. In this framework the Low Pressure Turbine (LPT) is known to be a key component since it has a major effect on specific fuel consumption (SFC). Modern aerodynamic design of LPTs for civil aircraft engines has reached high levels of quality, but new engine data, after first engine tests, often cannot achieve the expected performance. Further work on the modules is usually required, with additional costs and time spent to reach the quality level needed to enter in service. The reported study is aimed at understanding some of the causes for this deficit and how to solve some of the highlighted problems. In a real engine, the LPT module works under conditions which differ from those described in the analyzed numerical model: the definition of the geometry cannot be so accurate, a priori unknown values for boundary conditions data are often assumed, complex physical phenomena are seldom taken into account, operating cycle may differ from the design intent due to a non-optimal coupling with other engine components. Moreover, variations are present among different engines of the same family, manufacturing defects increase the uncertainty and, finally, deterioration of the components occurs during service. Research projects and several studies carried out by the authors lead to the conclusion that being able to design a module whose performance is less sensitive to variations (Robust LPT) brings advantages not only when the engine performs under strong off-design conditions but also, due to the abovementioned unknowns, near the design point as well. Concept and Preliminary Design phases are herein considered, highlighting the results arising from sensibility studies and their impact on the final designed robust configuration. Module performance is afterward estimated using a statistical approach.
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Hura, Harjit S., John Joseph, and Dave E. Halstead. "Reynolds Number Effects in a Low Pressure Turbine." In ASME Turbo Expo 2012: Turbine Technical Conference and Exposition. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/gt2012-68501.
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This paper reports the results of an experimental and analytical study of Reynolds number (Re) effect on Low Pressure Turbine (LPT) performance. LPTs suffer both a loss in efficiency and flow capacity at altitude due to thicker boundary layers and higher viscous losses. Boundary layer separation can occur in highly loaded and/or high lift designs. The magnitude of the effect is stronger for smaller engines being designed for regional jets which may have cruising altitudes above 50K feet. There is a general lack of knowledge about performance degradation in commercial LPTs under these conditions. A test program was undertaken in a low pressure 3 stage axial turbine to quantify the effect of low Re on efficiency and flow lapse rate. Rig inlet pressures were varied from 0.27E+5 N/m2 (4 psia) to 4.40E+5 N/m2 (65 psia) to achieve over a 15 fold variation in Re. The chord based average Re varied from 30000 to 500000. Efficiency and flow function lapse of over 5% was measured. The fall off was non-linear with a rapid loss occurring at Re below 100000. 3D CFD analysis was conducted in parallel to predict overall performance but also understand loss details within the blade rows. Measured inlet profiles of total pressure, temperature and air angle, and exit static pressure were used as boundary conditions. Leakages and purge flows were modeled as source terms. A turbulence transition model and wall integration grids was used. The CFD results corroborate the test findings on the overall efficiency and flow capacity lapse rate. Analysis of blade row performance at high and low Re shows a sharp increase in profile loss at low Re.
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Bolyukh, Vladimir F., and Igor I. Katkov. "Influence of the Form of Pulse of Excitation on the Speed and Power Parameters of the Linear Pulse Electromechanical Converter of the Induction Type." In ASME 2019 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2019. http://dx.doi.org/10.1115/imece2019-10388.
Full textAbstract:
Abstract Linear pulse electromechanical converters (LPEC) of induction type allow providing a high speed of the actuating element in the short active section and creating powerful power impulses with its insignificant movement. One of the ways to improve the electromechanical indicators of LPEC is the formation of current excitation pulses in the inductor using electronic power supply circuits containing a capacitive energy storage device. This publication is a continuation of our previous work on the influence of different parameters and conditions on the performance of LPEC. Using the developed chain mathematical model, recurrent relations are obtained for calculating the interconnected electromagnetic, mechanical and thermal parameters of LPEC. It has been established that the speed and power electromechanical indicators of LPEC with aperiodic excitation pulse are better than those of LPEC with unipolar excitation, but worse than those of LPEC with oscillating-damped excitation pulse. LPEC with a unipolar excitation pulse, by the end of the working cycle, the smallest temperatures of the inductor and the armature are observed, while for LPEC with a oscillating-damped excitation pulse, the greatest efficiency is ensured, being 24.88%. The highest speed and power electromechanical indicators are provided at LPEC with a step-aperiodic excitation pulse. Experimental studies of LPEC were conducted when operating as an electromechanical accelerator and a shock-power device. In studies of LPEC, a piezoelectric transducer was used as a shock-power device, which converted mechanical vibrations arising from the impact of the striker on the impact plate into electrical signals. In studies of LPEC, a displacement sensor was used as an electromechanical accelerator. It was established experimentally that the movement of the armature begins with a delay relative to the moment of occurrence of the current pulse and is almost linear in the initial part of the acceleration.
Reports on the topic "LptC"
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Watson, Kathleen. LPTA Versus Tradeoff: How Procurement Methods Can Impact Contract Performance. Fort Belvoir, VA: Defense Technical Information Center, June 2015. http://dx.doi.org/10.21236/ad1009457.
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Oldenburg, Curtis M., and Robert J. Budnitz. Low-Probability High-Consequence (LPHC) Failure Events in Geologic Carbon Sequestration Pipelines and Wells: Framework for LPHC Risk Assessment Incorporating Spatial Variability of Risk. Office of Scientific and Technical Information (OSTI), August 2016. http://dx.doi.org/10.2172/1332329.
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Gansler, Jacques S., and William Lucyshyn. The DoD's Use of Lowest Price Technically Acceptable (LPTA) Price Selection. Fort Belvoir, VA: Defense Technical Information Center, September 2013. http://dx.doi.org/10.21236/ada590274.
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Goncharoff, V., E. VonColln, and R. Morris. Efficient Calculation of Spectral Tilt from Various LPC Parameters,. Fort Belvoir, VA: Defense Technical Information Center, May 1996. http://dx.doi.org/10.21236/ada308580.
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Kang, George S., and David A. Heide. Transcoding Between Two DoD Narrowband Voice Encoding Algorithms (LPC-10 and MELP). Fort Belvoir, VA: Defense Technical Information Center, October 1999. http://dx.doi.org/10.21236/adb248890.
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Trebaol, George O., and Randy L. Heckman. Intelligibility Performance of the LPC-10 and APC/SQ Speech Algorithms in a Fading Environment. Fort Belvoir, VA: Defense Technical Information Center, February 1985. http://dx.doi.org/10.21236/ada166102.
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Mack, M., J. Tierney, and M. E. Boyle. The Intelligibility of Natural and LPC-Vocoded Words and Sentences Presented to Native and Non-Native Speakers of English. Fort Belvoir, VA: Defense Technical Information Center, July 1990. http://dx.doi.org/10.21236/ada226180.
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