The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
James J Collins - One of the best experts on this subject based on the ideXlab platform.
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bacterial charity work leads to population wide resistance
Nature, 2010Co-Authors: Henry H Lee, Michael Molla, Charles R Cantor, James J CollinsAbstract:The emergence of antibiotic-resistant bacterial strains is a growing threat in clinical environments, but the process by which they arise is not well understood. Experiments using a continuous culture of Escherichia coli exposed to increasing concentrations of an antibiotic show that a few spontaneous drug-resistant mutants can protect the majority of the population. These highly resistant isolates produce the Signalling Molecule indole, which activates drug efflux pumps and other protective mechanisms in susceptible kin. This altruism allows weaker constituents to survive and to have the chance of beneficial mutation. More work on the use of intracellular communication by bacteria may prove of value for the rational design of clinical interventions to control resistant bacterial infections. Bacteria regularly evolve antibiotic resistance, but little is known about this process at the population level. Here, a continuous culture of Escherichia coli facing increasing antibiotic levels is followed. Most isolates taken from this population are less antibiotic resistant than the population as a whole. A few highly resistant mutants provide protection to the less resistant constituents, in part by producing the Signalling Molecule indole, which serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates1,2,3,4,5,6,7. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part by producing indole, a Signalling Molecule generated by actively growing, unstressed cells8. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection9 whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.
Christopher D Maycock - One of the best experts on this subject based on the ideXlab platform.
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an efficient synthesis of the precursor of ai 2 the Signalling Molecule for inter species quorum sensing
Bioorganic & Medicinal Chemistry, 2011Co-Authors: Osvaldo S Ascenso, Joao C Marques, Ana Rita Santos, Karina B Xavier, Rita M Ventura, Christopher D MaycockAbstract:Autoinducer-2 (AI-2) is a Signalling Molecule for bacterial inter-species communication. A synthesis of (S)-4,5-dihydroxypentane-2,3-dione (DPD), the precursor of AI-2, is described starting from methyl glycolate. The key step was an asymmetric reduction of a ketone with (S)-Alpine borane. This new method was highly reproducible affording DPD for biological tests without contaminants. The biological activity was tested with the previously available assays and compared with a new method using an Escherichia coli reporter strain thus avoiding the use of the pathogenic Salmonella reporter.
Kristoffer Strom - One of the best experts on this subject based on the ideXlab platform.
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n1 methylnicotinamide is a Signalling Molecule produced in skeletal muscle coordinating energy metabolism
Scientific Reports, 2018Co-Authors: Kristoffer Strom, David Moralesalamo, Filip Ottosson, Anna Edlund, Line Hjort, Sine W Jorgensen, Peter Almgren, Yuedan Zhou, Marcos MartinrinconAbstract:Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.
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n 1 methylnicotinamide is a Signalling Molecule produced in skeletal muscle coordinating energy metabolism
Scientific Reports, 2018Co-Authors: Kristoffer Strom, David Moralesalamo, Filip Ottosson, Anna Edlund, Line Hjort, Sine W Jorgensen, Peter Almgren, Yuedan Zhou, Marcos MartinrinconAbstract:Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.
Bruno Lemaitre - One of the best experts on this subject based on the ideXlab platform.
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a secondary metabolite acting as a Signalling Molecule controls pseudomonas entomophila virulence
Cellular Microbiology, 2010Co-Authors: Isabelle Valletgely, Onya Opota, Audrey Boniface, Alexey Novikov, Bruno LemaitreAbstract:Pseudomonas entomophila is an entomopathogenic bacterium that is lethal to Drosophila melanogaster within 1-2 days of ingestion of high doses. Flies orally infected with P. entomophila rapidly succumb despite the induction of both local and systemic immune responses. Recent studies suggest that its virulence relies on its ability to cause irreversible damages to the intestinal epithelium, in contrast to what is observed with milder pathogenic bacteria such as Erwinia carotovora carotovora Ecc15 or Pseudomonas aeruginosa PA14. The GacS/GacA two-component system plays a key role in P. entomophila pathogenicity. Here, we report the identification of the pvf genes, whose products are involved in production of a secondary metabolite involved in P. entomophila virulence. A pvf mutant is impaired in its ability to persist within the gut, to trigger the fly immune responses and to inflict gut damages. The expression of several genes is affected in a pvf mutant, independently of the Gac system. Moreover, growing a pvf mutant in medium supplemented with supernatant extracts from either the wild-type strain or a gacA mutant restore its pathogenicity. Collectively, our results indicate that we identified genes involved in the synthesis of a Signalling Molecule that controls P. entomophila virulence independently from the Gac system.
Joseph J Kieber - One of the best experts on this subject based on the ideXlab platform.
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1-Aminocyclopropane-1-carboxylic acid as a Signalling Molecule in plants
AoB Plants, 2013Co-Authors: G. M. Yoon, Joseph J KieberAbstract:Ethylene influences many aspects of plant growth and development including germination, leaf and floral senescence and abscission, fruit ripening, and the response to abiotic and biotic stress. The pathways involved in the biosynthesis of and response to ethylene have been elucidated. The first committed and generally rate-limiting step in ethylene biosynthesis is the conversion of S-adenosyl-methionine to 1-aminocyclopropane-1-carboxylic acid (ACC) by ACC synthase (ACS). This enzyme is encoded by a gene family in most plants and is subject to both transcriptional and post-transcriptional control in response to numerous endogenous and environmental cues. In addition to its well-described function as the immediate precursor of ethylene, recent studies suggest an alternative, non-canonical role for ACC. These studies found that in some contexts, chemical inhibitors of ethylene biosynthesis caused effects on root cell expansion that were not observed when ethylene perception or Signalling was disrupted, suggesting that ACC, but not ethylene, played a role in these specific processes. Furthermore, mutation of all eight ACS genes in Arabidopsis was found to result in embryo lethality, in contrast to the relatively modest developmental effects of null mutants in the ethylene Signalling components. This divergence suggests that ACC may play a role as a Signalling Molecule in plants. Here, we first review the ethylene biosynthesis pathway and then discuss these studies suggesting an independent role of ACC as a Signalling Molecule.
