The Experts below are selected from a list of 255165 Experts worldwide ranked by ideXlab platform
Klaus Aktories - One of the best experts on this subject based on the ideXlab platform.
-
ADP-Ribosylation and Cross-Linking of Actin by Bacterial Protein Toxins.
Handbook of experimental pharmacology, 2016Co-Authors: Klaus Aktories, Carsten Schwan, Alexander E. LangAbstract:Actin and the actin cytoskeleton play fundamental roles in host–pathogen interactions. Proper function of the actin cytoskeleton is crucial for innate and acquired immune defense. Bacterial toxins attack the actin cytoskeleton by targeting regulators of actin. Moreover, actin is directly modified by various Bacterial Protein toxins and effectors, which cause ADP-ribosylation or cross-linking of actin. Modification of actin can result in inhibition or stimulation of actin polymerization. Toxins, acting directly on actin, are reviewed.
-
Rho-modifying Bacterial Protein toxins
Pathogens and disease, 2015Co-Authors: Klaus AktoriesAbstract:Rho Proteins are targets of numerous Bacterial Protein toxins, which manipulate the GTP-binding Proteins by covalent modifications, including ADP ribosylation, glycosylation, adenylylation, proteolytic cleavage and deamidation. Bacterial toxins are important virulence factors but are also potent and efficient pharmacological tools to study the physiological functions of their eukaryotic targets. Recent studies indicate that amazing variations exist in the molecular mechanisms by which toxins attack Rho Proteins, which are discussed here.
-
Bacterial Protein Toxins Acting on Small GTPases
Ras Superfamily Small G Proteins: Biology and Mechanisms 1, 2014Co-Authors: Klaus Aktories, Gudula SchmidtAbstract:Numerous Bacterial Protein toxins and effectors target eukaryotic cells by covalent modification of low molecular mass GTP-binding Proteins to manipulate their switch functions. Frequent targets are Rho, Ras, and Rab Proteins which are modified by ADP-ribosylation, adenylylation, mono-O-glycosylation, deamidation, transglutamination, phosphocholination, and proteolytic cleavage. Thereby, the GTPases are activated or inactivated. Other Bacterial effectors manipulate the cellular functions of small GTPases by mimicking endogenous regulators of the switch Proteins. They act as guanine nucleotide exchange factors (GEFs) or GTPase-activating Proteins (GAPs). The chapter describes the Bacterial toxins and effectors and discusses the functional consequences of their actions.
-
14 Bacterial Protein Toxins as Tools in Cell Biology and Pharmacology
Cellular Microbiology, 2014Co-Authors: Klaus AktoriesAbstract:At least four properties of Bacterial Protein toxins make them suitable as cell biological and pharmacological tools. First, the toxins enter cells without damaging the cell integrity. Second, the toxins possess high specificity. A high cell specificity is most often based on a toxin-specific membrane-binding domain and on specific receptors present on the surface of eukaryotic target cells. Actin, another important eukaryotic substrate for ADP-ribosylation by Bacterial toxins, is not a GTP-binding Protein but an ATP-binding Protein. Because all these nucleotide-binding Proteins are functionally important cellular Proteins, the toxins, which allow their selective covalent modification, are widely used as tools. The actin cytoskeleton is the target of various Bacterial toxins that affect the microfilament Protein either directly by ADP-ribosylation or indirectly by modifying the regulatory mechanisms involved in the organization of the actin cytoskeleton. Actin, which is one of the most abundant Proteins in eukaryotic cells, is the major component of the microfilament system. The toxin effect should occur with some delay of at least 15 to 30 min. This time is necessary for the translocation of the toxin. Moreover, it should be tested whether actin is in fact ADP-ribosylated by the toxin. Hydrolysis of bound GTP terminates the active state of the GTPases. It has been shown that especially Rho subfamily GTPases are targets for Bacterial Protein toxins. Recently, the genes for toxins were introduced into some crop plants in an effort to protect them from insect attack.
-
Bacterial Protein toxins that modify host regulatory GTPases
Nature Reviews Microbiology, 2011Co-Authors: Klaus AktoriesAbstract:Many Bacterial pathogens produce Protein toxins and effectors that target host regulatory GTPases such as those belonging to the RHO family, which control the actin cytoskeleton. In this Review, Aktories discusses the mechanisms used by these Bacterial Proteins to modulate the activity of host GTPases, with a focus on covalent modifications. Many Bacterial pathogens produce Protein toxins and effectors that target host regulatory GTPases such as those belonging to the RHO family, which control the actin cytoskeleton. As a result, the pathogens weaken the epithelial and endothelial barriers and manipulate the host immune response, leading to Bacterial invasion and dissemination in tissues. Regulatory GTPases switch between an active, GTP-bound form that is attached to the cell membrane through an isoprenyl moiety, and an inactive, GDP-bound form in the cytosol. This GTPase cycle is controlled by various classes of host Proteins such as guanine nucleotide exchange factors (GEFs), GTPase-activating Proteins (GAPs) and guanine nucleotide dissociation inhibitors (GDIs). Various Bacterial effectors can affect the activity of host GTPases by mimicking host regulators of the GTPase cycle through mechanisms that do not involve covalent modifications of the target Proteins. For example, effectors of the SopE and WXXXE families act in a GEF-like manner, whereas YopE from Yersinia pseudotuberculosis is a GAP mimic. Other Bacterial Proteins modulate the activity of regulatory GTPases by covalent modifications. Bacterial Protein toxins of the C3 family inhibit the regulatory activity of RHO-family Proteins by ADP-ribosylation of a specific amino acid residue, whereas the toxin complex (Tc) toxin TccC5 from Photorhabdus luminescens stimulates the activity of RHO-family Proteins by ADP-ribosylating a different residue. Various Protein toxins from Clostridium spp. inactivate regulatory GTPases by addition of a glucose or an N -acetylglucosamine residue. The adenylylation (also known as 'AMP-ylation') of RHO-family Proteins by the toxins VopS and IbpA (immunoglobulin-binding Protein A) from Vibrio parahemolyticus and Histophilus somni , respectively, leads to inhibition of downstream signalling of these host GTPases, whereas the same reaction on a different amino acid residue, catalysed by DrrA from Legionella pneumophila , leads to stimulation of RAB1A regulatory activity. YopT from Yersinia spp. is a protease that cleaves RHO-family Proteins directly upstream of the carboxy-terminal cysteine residue to which the isoprenyl moiety is attached. As a result, the RHO-family Protein is released from the membrane and therefore inactivated. RHO-family Proteins can be persistently activated by deamidation and transglutamination catalysed by the cytotoxic necrotizing factors (Cnfs) of Escherichia coli and Y. pseudotuberculosis and the dermonecrotizing toxin (Dnt) of Bordetella spp. In addition, Pasteurella multocida toxin (Pmt) activates heterotrimeric guanine-nucleotide-binding (G) Proteins, a family of multisubunit regulatory GTPases, by deamidation. Many Bacterial pathogens produce Protein toxins to outmanoeuvre the immune system of the host. Some of these Proteins target regulatory GTPases such as those belonging to the RHO family, which control the actin cytoskeleton of the host cell. In this Review, I discuss a diversity of mechanisms that are used by Bacterial effectors and toxins to modulate the activity of host GTPases, with a focus on covalent modifications such as ADP-ribosylation, glucosylation, adenylylation, proteolysis, deamidation and transglutamination.
Anastassios Economou - One of the best experts on this subject based on the ideXlab platform.
-
Bacterial Protein secretion through the translocase nanomachine
Nature Reviews Microbiology, 2007Co-Authors: Effrosyni Papanikou, Spyridoula Karamanou, Anastassios EconomouAbstract:The Sec pathway, which transports Proteins across membranes, is ubiquitous and essential for viability in all three domains of life. At the core of the pathway is the translocase, a dynamic nanomachine that catalyses transmembrane crossing. This Review considers the latest data on the structure and function of the Bacterial Sec translocase. All cells must traffic Proteins across their membranes. This essential process is responsible for the biogenesis of membranes and cell walls, motility and nutrient scavenging and uptake, and is also involved in pathogenesis and symbiosis. The translocase is an impressively dynamic nanomachine that is the central component which catalyses transmembrane crossing. This complex, multi-stage reaction involves a cascade of inter- and intramolecular interactions that select, sort and target polypeptides to the membrane, and use energy to promote the movement of these polypeptides across — or their lateral escape and integration into — the phospholipid bilayer, with high fidelity and efficiency. Here, we review the most recent data on the structure and function of the translocase nanomachine. The Sec machinery is essential for life. All cells need to assemble phospholipid bilayer membranes, which have embedded Proteins. In bacteria, the Sec pathway catalyses most of the load of Protein secretion and acts as the front end for several subsequent Protein-sorting and sub-cellular-targeting machines. A combination of membrane-embedded and soluble factors that contribute to pre-Protein targeting and translocation are described. A membrane-embedded pre-Protein-conducting channel and an ATPase motor lie at its core. Atomic resolution structures of the pre-Protein-conducting channel, its ATPase motor and targeting chaperones are available. The Protein-conducting channel is composed of several tilted and straight helices of varying lengths and is gated by a periplasmic plug. It has a well-characterized closed state and an anticipated open state that is expected to result from dilation. Metabolic energy in the form of both ATP and the proton motive force is used to power pre-Protein movement through the translocase machine. The available data allow for a synthesis of multiple sub-reactions into a coherent model. This model describes how the translocase recognizes secretory Proteins at specific sites and how it subsequently promotes Protein export by a series of distinct energy-driven conformational states.
-
Bacterial Protein secretion through the translocase nanomachine
Nature Reviews Microbiology, 2007Co-Authors: Effrosyni Papanikou, Spyridoula Karamanou, Anastassios EconomouAbstract:The Sec pathway, which transports Proteins across membranes, is ubiquitous and essential for viability in all three domains of life. At the core of the pathway is the translocase, a dynamic nanomachine that catalyses transmembrane crossing. This Review considers the latest data on the structure and function of the Bacterial Sec translocase.
-
Sec, drugs and rock'n'roll: antibiotic targeting of Bacterial Protein translocation.
Emerging Therapeutic Targets, 2001Co-Authors: Anastassios EconomouAbstract:A large number of Bacterial Proteins are active in extracytoplasmic locations. Targeting and membrane translocation of the vast majority of these secretory and membrane polypeptides is mediated by the Sec pathway. Protein secretion requires the co-ordinated and sequential action of targeting factors on the cis-side of the membrane, a complex membrane-embedded Protein translocase and maturation enzymes on the trans-side. Recently, significant advances in the molecular genetics and biochemistry of the Sec pathway have revealed that several of the Sec pathway components are essential for Bacterial viability and/or pathogenicity. Moreover, several biochemical assays and structural insights have become available. Importantly, some of the Sec components are unique to bacteria. These developments raise the possibility that the Bacterial Protein translocase and other Sec pathway components could become formidable targets for antiBacterial drug discovery.
Anders Skrede - One of the best experts on this subject based on the ideXlab platform.
-
technical quality of dog food and salmon feed containing different Bacterial Protein sources and processed by different extrusion conditions
Animal Feed Science and Technology, 2007Co-Authors: Margareth Overland, Odd Helge Romarheim, Oystei Ahlstrom, Trond Storebakke, Anders SkredeAbstract:Abstract The effect of basic Bacterial Protein meal (BPM) and Bacterial Protein meal homogenate (HOM) on length, expansion, density, sinking rate, fat leakage, durability, and breaking force of extruded dog food and salmon feed exposed to mild and moderate processing conditions was evaluated. The treatment consisted of a control diet and four test diets where high-quality (low temperature dried; LT) fish meal was partly replaced with either 25 or 50 g BPM or HOM kg −1 . The differences in processing characteristics were obtained by a combination of conditioner and extruder adjustments. Fat was added to the extruded diets by vacuum coating. In the dog diets, the inclusion of BPM and HOM resulted in shorter pellets with increased diametric expansion, and reduced dust percentage, sinking rate and breaking force, with the effect being in general greatest with the highest concentration. In general, moderate feed processing resulted in increased pellet length and expansion while sinking rate and fat leakage decreased in both the BPM and HOM diets. Neither BPM nor HOM affected fat leakage, but fat leakage decreased by moderate processing. In the salmon diets, dietary BPM and HOM increased density and breaking force, but decreased durability and had no effect on sinking rate or fat leakage of the extruded salmon pellets. A significant interaction between feed processing and Bacterial Protein source was found for pellet length and diameter. Moderate feed processing increased pellet length in the BPM diets but reduced pellet length and increased pellet expansion in the HOM diet. Moderate processing decreased durability and sinking rate of the pellets. Coefficients of total tract apparent digestibility (CTTAD) of the control, 50 g kg −1 BPM and 50 g kg −1 HOM dog diets exposed to mild and moderate feed processing were determined in mink. There was no significant effects of type of diet or feed processing on CTTAD of major dietary components. The results demonstrate that low amounts of BPM and HOM influenced the technical quality of extruded diets for dogs and salmon. The effect of BPM and HOM was different in dog food with higher starch content compared to the salmon feed with lower starch content, and was dependent on extrusion conditions.
-
Effect of dietary Bacterial Protein or L-tryptophan supplementation on welfare and growth performance in silver fox.
Canadian Journal of Animal Science, 2007Co-Authors: Hilde Faaland Schøyen, Kirsti Rouvinen-watt, Erik Höglund, K. Peter Stone, Anders SkredeAbstract:The suitability of Bacterial Protein meal as a feed ingredient in silver fox diets was examined in an experiment comprising 72 juvenile silver foxes. Bacterial Protein meal has a high content of tryptophan, which is the precursor for the neurotransmitter serotonin. The biological hypothesis on which this study was premised was that increased brain serotonin production reduces the fear response, which may lead to better welfare and performance through lower energy expenditure related to fear-induced defensive responses. The effect of substituting 15% fish meal with Bacterial Protein meal was measured by two behavioural tests, growth performance and fur quality, by comparison with a control diet and a diet supplemented with a high level of synthetic tryptophan. The welfare of the foxes fed the diet supplemented with synthetic tryptophan was considered to be improved, as they used shorter time to approach feed in the presence of a person; thus displayed less fear, than the other two groups after treatment. W...
-
Excretion of purine base derivatives after intake of Bacterial Protein meal in pigs
Livestock Science, 2007Co-Authors: A. L. F. Hellwing, Anne-helene Tauson, Anders SkredeAbstract:Abstract Bacterial Protein meal has a high content of Protein but also of RNA and DNA. Sixteen barrows were allocated to four diets containing increasing levels of Bacterial Protein meal (BPM), from weaning to 80 kg live weight, to evaluate whether the RNA and DNA contents of BPM influenced the retention of nitrogen. It was hypothesised that an increased intake of RNA and DNA would lead to an increased urinary excretion of purine base derivatives and increased plasma concentrations. Retention of nitrogen was unaffected by dietary content of BPM ( P = 0.08) and the urinary excretion of purine base derivatives increased with increasing dietary content of BPM. No differences in fasting plasma concentration of uric acid, xanthine and hypoxanthine were observed. It can therefore be concluded that increasing levels of dietary BPM maintained Protein accretion and led to changes in excretion of purine derivatives, but did not cause uricogenic effects in the pigs.
-
Growth Performance and Ileal and Total Tract Amino Acid Digestibility in Broiler Chickens Fed Diets Containing Bacterial Protein Produced on Natural Gas
Poultry science, 2007Co-Authors: Hilde Faaland Schøyen, Kirsti Rouvinen-watt, H. Hetland, Anders SkredeAbstract:ABSTRACT A total of 180 broiler chickens were fed 1 of 3 diets from day-old to slaughter at 35 d: a control diet with 35% soybean meal (SOY) or diets in which either 6% basic Bacterial Protein meal (BBP) or 6% autolysed Bacterial Protein meal (AUT) partially replaced soybean meal Protein. Ileal and total tract apparent amino acid digestibility were examined in 5 chickens per diet using TiO2as an inert marker. Chickens fed the diets with Bacterial Protein had higher weight gain and feed consumption than control chicks during the first 3 wk, but there were no differences in growth or feed intake during the last 2 wk or during the total experimental period. The birds fed the BBP diet showed more efficient feed conversion compared with chickens fed the SOY and AUT diets. Litter quality at 5 wk was poorer in pens where the chickens were fed the AUT diet compared with the other 2 treatments. There were no differences among diets in the dressing percentage. Ileal amino acid digestibility at 5 wk of age revealed only minor differences between diets. There was a tendency toward lower ileal digestibility (0.12 > P> 0.07) of Arg, Lys, Met, and Phe in the AUT diet compared with the SOY diet, whereas there were no differences between the SOY and BBP diets. Total tract amino acid digestibilities at 5 wk were similar or slightly lower than the ileal digestibilities within diets. Total tract amino acid digestibility at 2 wk was similar to the total tract amino acid digestibility at 5 wk. The diets containing Bacterial Protein showed lower total tract digestibility of most amino acids compared with the SOY diet. It was concluded that 6% of either basic or autolysed Bacterial Protein can replace soybean meal in diets for broiler chickens without impairing growth performance, and the basic Bacterial Protein seemed to be a slightly better substitute than the autolysed Bacterial Protein.
-
Effects of autolysis and hydrolysis of Bacterial Protein meal grown on natural gas on chemical characterization and amino acid digestibility
Aquaculture, 2005Co-Authors: Hilde Faaland Schøyen, Janna Randi Kringeland Frøyland, Stefan Sahlstrøm, Svein Halvor Knutsen, Anders SkredeAbstract:Bacterial Protein meal produced from bacteria cultured on natural gas is a novel alternative Protein source. Several products with different nutritional features were made from basic Bacterial Protein meal (BBP) by autolysis and hydrolysis. These products were investigated in terms of chemical characterization of the Protein fraction and amino acid digestibility, using mink as model animal. The BBP, autolysate, autolysate extract, hydrolysate extract, and the insoluble byproducts of the latter two exhibited considerable differences in amino acid profile and great differences in Protein solubility and molecular size. Apparent digestibility of arginine, lysine and methionine was high in all products, while cysteine digestibility was low. Compared to BBP, the extracts of autolysate and hydrolysate showed higher digestibility of most amino acids. All products of autolysis showed higher tryptophan digestibility but lower cysteine digestibility compared to BBP. The byproducts from autolysate and hydrolysate with low Protein solubility and large molecule size had lower amino acid digestibility than the extracts. Autolysis and hydrolysis and separation into extracts of high Protein solubility and small molecular size increased amino acid digestibility of the Bacterial Protein.
Ivan Mijakovic - One of the best experts on this subject based on the ideXlab platform.
-
Evolution of Bacterial Protein-tyrosine kinases and their relaxed specificity toward substrates
Genome Biology and Evolution, 2014Co-Authors: Lei Shi, C. Grangeasse, Lorena Kolar-znika, Ana Boskovic, Fanny Jadeau, Christophe Combet, Damjan Franjevic, Emmanuel Talla, Ivan MijakovicAbstract:It has often been speculated that Bacterial Protein-tyrosine kinases (BY-kinases) evolve rapidly and maintain relaxed substrate specificity to quickly adopt new substrates when evolutionary pressure in that direction arises. Here, we report a phylogenomic and biochemical analysis of BY-kinases, and their relationship to substrates aimed to validate this hypothesis. Our results suggest that BY-kinases are ubiquitously distributed in Bacterial phyla and underwent a complex evolutionary history, affected considerably by gene duplications and horizontal gene transfer events. This is consistent with the fact that the BY-kinase sequences represent a high level of substitution saturation and have a higher evolutionary rate compared with other Bacterial genes. On the basis of similarity networks, we could classify BY kinases into three main groups with 14 subgroups. Extensive sequence conservation was observed only around the three canonical Walker motifs, whereas unique signatures proposed the functional speciation and diversification within some subgroups. The relationship between BY-kinases and their substrates was analyzed using a ubiquitous substrate (Ugd) and some Firmicute-specific substrates (YvyG and YjoA) from Bacillus subtilis. No evidence of coevolution between kinases and substrates at the sequence level was found. Seven BY-kinases, including well-characterized and previously uncharacterized ones, were used for experimental studies. Most of the tested kinases were able to phosphorylate substrates from B. subtilis (Ugd, YvyG, and YjoA), despite originating from very distant bacteria. Our results are consistent with the hypothesis that BY-kinases have evolved relaxed substrate specificity and are probably maintained as rapidly evolving platforms for adopting new substrates.
-
BYKdb: the Bacterial Protein tYrosine Kinase database.
Nucleic Acids Research, 2012Co-Authors: Fanny Jadeau, C. Grangeasse, Ivan Mijakovic, Lei Shi, Gilbert Deléage, Christophe CombetAbstract:Bacterial tyrosine-kinases share no resemblance with their eukaryotic counterparts and they have been unified in a new Protein family named BY-kinases. These enzymes have been shown to control several biological functions in the Bacterial cells. In recent years biochemical studies, sequence analyses and structure resolutions allowed the deciphering of a common signature. However, BY-kinase sequence annotations in primary databases remain incomplete. This prompted us to develop a specialized database of computer-annotated BY-kinase sequences: the Bacterial Protein tyrosine-kinase database (BYKdb). BY-kinase sequences are first identified, thanks to a workflow developed in a previous work. A second workflow annotates the UniProtKB entries in order to provide the BYKdb entries. The database can be accessed through a web interface that allows static and dynamic queries and offers integrated sequence analysis tools. BYKdb can be found at http://bykdb.ibcp.fr.
Christophe Combet - One of the best experts on this subject based on the ideXlab platform.
-
Evolution of Bacterial Protein-tyrosine kinases and their relaxed specificity toward substrates
Genome Biology and Evolution, 2014Co-Authors: Lei Shi, C. Grangeasse, Lorena Kolar-znika, Ana Boskovic, Fanny Jadeau, Christophe Combet, Damjan Franjevic, Emmanuel Talla, Ivan MijakovicAbstract:It has often been speculated that Bacterial Protein-tyrosine kinases (BY-kinases) evolve rapidly and maintain relaxed substrate specificity to quickly adopt new substrates when evolutionary pressure in that direction arises. Here, we report a phylogenomic and biochemical analysis of BY-kinases, and their relationship to substrates aimed to validate this hypothesis. Our results suggest that BY-kinases are ubiquitously distributed in Bacterial phyla and underwent a complex evolutionary history, affected considerably by gene duplications and horizontal gene transfer events. This is consistent with the fact that the BY-kinase sequences represent a high level of substitution saturation and have a higher evolutionary rate compared with other Bacterial genes. On the basis of similarity networks, we could classify BY kinases into three main groups with 14 subgroups. Extensive sequence conservation was observed only around the three canonical Walker motifs, whereas unique signatures proposed the functional speciation and diversification within some subgroups. The relationship between BY-kinases and their substrates was analyzed using a ubiquitous substrate (Ugd) and some Firmicute-specific substrates (YvyG and YjoA) from Bacillus subtilis. No evidence of coevolution between kinases and substrates at the sequence level was found. Seven BY-kinases, including well-characterized and previously uncharacterized ones, were used for experimental studies. Most of the tested kinases were able to phosphorylate substrates from B. subtilis (Ugd, YvyG, and YjoA), despite originating from very distant bacteria. Our results are consistent with the hypothesis that BY-kinases have evolved relaxed substrate specificity and are probably maintained as rapidly evolving platforms for adopting new substrates.
-
BYKdb: the Bacterial Protein tYrosine Kinase database.
Nucleic Acids Research, 2012Co-Authors: Fanny Jadeau, C. Grangeasse, Ivan Mijakovic, Lei Shi, Gilbert Deléage, Christophe CombetAbstract:Bacterial tyrosine-kinases share no resemblance with their eukaryotic counterparts and they have been unified in a new Protein family named BY-kinases. These enzymes have been shown to control several biological functions in the Bacterial cells. In recent years biochemical studies, sequence analyses and structure resolutions allowed the deciphering of a common signature. However, BY-kinase sequence annotations in primary databases remain incomplete. This prompted us to develop a specialized database of computer-annotated BY-kinase sequences: the Bacterial Protein tyrosine-kinase database (BYKdb). BY-kinase sequences are first identified, thanks to a workflow developed in a previous work. A second workflow annotates the UniProtKB entries in order to provide the BYKdb entries. The database can be accessed through a web interface that allows static and dynamic queries and offers integrated sequence analysis tools. BYKdb can be found at http://bykdb.ibcp.fr.