The Experts below are selected from a list of 9456 Experts worldwide ranked by ideXlab platform
Sarah M Fortune - One of the best experts on this subject based on the ideXlab platform.
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Bacterial genome wide association identifies novel factors that contribute to ethionamide and prothionamide susceptibility in mycobacterium tuberculosis
Mbio, 2019Co-Authors: Nathan D Hicks, Allison F Carey, Jian Yang, Yanlin Zhao, Sarah M FortuneAbstract:In Mycobacterium tuberculosis, recent genome-wide association studies have identified a novel constellation of mutations that are correlated with high-level drug resistances. Interpreting the functional importance of the new resistance-associated mutations has been complicated, however, by a lack of experimental validation and a poor understanding of the epistatic factors influencing these correlations, including strain background and programmatic variation in treatment regimens. Here we perform a genome-wide association analysis in a panel of Mycobacterium tuberculosis strains from China to identify variants correlated with resistance to the second-line prodrug ethionamide (ETH). Mutations in a Bacterial monooxygenase, Rv0565c, are significantly associated with ETH resistance. We demonstrate that Rv0565c is a novel activator of ETH, independent of the two known activators, EthA and MymA. Clinically prevalent mutations abrogate Rv0565c function, and deletion of Rv0565c confers a consistent fitness benefit on M. tuberculosis in the presence of partially inhibitory doses of ETH. Interestingly, Rv0565c activity affects susceptibility to prothionamide (PTH), the ETH analog used in China, to a greater degree. Further, clinical isolates vary in their susceptibility to both ETH and PTH, to an extent that correlates with the total expression of ETH/PTH activators (EthA, MymA, and Rv0565c). These results suggest that clinical strains considered susceptible to ETH/PTH are not equally fit during treatment due to both Rv0565c mutations and more global variation in the expression of the prodrug activators.IMPORTANCE Phenotypic antibiotic susceptibility testing in Mycobacterium tuberculosis is slow and cumbersome. Rapid molecular diagnostics promise to help guide therapy, but such assays rely on complete knowledge of the molecular determinants of altered antibiotic susceptibility. Recent genomic studies of antibiotic-resistant M. tuberculosis have identified several candidate loci beyond those already known to contribute to antibiotic resistance; however, efforts to provide experimental validation have lagged. Our study identifies a gene (Rv0565c) that is associated with resistance to the second-line antibiotic ethionamide at a population level. We then use Bacterial Genetics to show that the variants found in clinical strains of M. tuberculosis improve Bacterial survival after ethionamide exposure.
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Bacterial Genome-Wide Association Identifies Novel Factors That Contribute to Ethionamide and Prothionamide Susceptibility in Mycobacterium tuberculosis
American Society for Microbiology, 2019Co-Authors: Nathan D Hicks, Allison F Carey, Jian Yang, Yanlin Zhao, Sarah M FortuneAbstract:Phenotypic antibiotic susceptibility testing in Mycobacterium tuberculosis is slow and cumbersome. Rapid molecular diagnostics promise to help guide therapy, but such assays rely on complete knowledge of the molecular determinants of altered antibiotic susceptibility. Recent genomic studies of antibiotic-resistant M. tuberculosis have identified several candidate loci beyond those already known to contribute to antibiotic resistance; however, efforts to provide experimental validation have lagged. Our study identifies a gene (Rv0565c) that is associated with resistance to the second-line antibiotic ethionamide at a population level. We then use Bacterial Genetics to show that the variants found in clinical strains of M. tuberculosis improve Bacterial survival after ethionamide exposure.In Mycobacterium tuberculosis, recent genome-wide association studies have identified a novel constellation of mutations that are correlated with high-level drug resistances. Interpreting the functional importance of the new resistance-associated mutations has been complicated, however, by a lack of experimental validation and a poor understanding of the epistatic factors influencing these correlations, including strain background and programmatic variation in treatment regimens. Here we perform a genome-wide association analysis in a panel of Mycobacterium tuberculosis strains from China to identify variants correlated with resistance to the second-line prodrug ethionamide (ETH). Mutations in a Bacterial monooxygenase, Rv0565c, are significantly associated with ETH resistance. We demonstrate that Rv0565c is a novel activator of ETH, independent of the two known activators, EthA and MymA. Clinically prevalent mutations abrogate Rv0565c function, and deletion of Rv0565c confers a consistent fitness benefit on M. tuberculosis in the presence of partially inhibitory doses of ETH. Interestingly, Rv0565c activity affects susceptibility to prothionamide (PTH), the ETH analog used in China, to a greater degree. Further, clinical isolates vary in their susceptibility to both ETH and PTH, to an extent that correlates with the total expression of ETH/PTH activators (EthA, MymA, and Rv0565c). These results suggest that clinical strains considered susceptible to ETH/PTH are not equally fit during treatment due to both Rv0565c mutations and more global variation in the expression of the prodrug activators
Alexander S Pym - One of the best experts on this subject based on the ideXlab platform.
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impact of Bacterial Genetics on the transmission of isoniazid resistant mycobacterium tuberculosis
PLOS Pathogens, 2006Co-Authors: Sebastien Gagneux, Marcos Burgos, Kathryn Deriemer, Antonio Enciso, Samira Munoz, Phillip C Hopewell, Peter M Small, Alexander S PymAbstract:Understanding the ecology of drug-resistant pathogens is essential for devising rational programs to preserve the effective lifespan of antimicrobial agents and to abrogate epidemics of drug-resistant organisms. Mathematical models predict that strain fitness is an important determinant of multidrug-resistant Mycobacterium tuberculosis transmission, but the effects of strain diversity have been largely overlooked. Here we compared the impact of resistance mutations on the transmission of isoniazid-resistant M. tuberculosis in San Francisco during a 9-y period. Strains with a KatG S315T or inhA promoter mutation were more likely to spread than strains with other mutations. The impact of these mutations on the transmission of isoniazid-resistant strains was comparable to the effect of other clinical determinants of transmission. Associations were apparent between specific drug resistance mutations and the main M. tuberculosis lineages. Our results show that in addition to host and environmental factors, strain genetic diversity can influence the transmission dynamics of drug-resistant bacteria.
Geraldine Laloux - One of the best experts on this subject based on the ideXlab platform.
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shedding light on the cell biology of the predatory bacterium bdellovibrio bacteriovorus
Frontiers in Microbiology, 2020Co-Authors: Geraldine LalouxAbstract:Bdellovibrio bacteriovorus is a predatory bacterium that feeds upon and proliferates inside other Gram-negative bacteria. Upon entry into the periplasmic space of the prey envelope, B. bacteriovorus initiates an exquisite developmental program in which it digests the host resources and grows as a filament, which eventually divides in a non-binary manner, releasing a variable number of daughter cells. The progeny then escape from the prey ghost to encounter new victims and resume the predation cycle. Owing to its unique biology, B. bacteriovorus undoubtedly represents an attractive model to unravel novel mechanisms of Bacterial cell cycle control and cellular organization. Yet, the molecular factors behind the sophisticated lifestyle of this micro-predator are still mysterious. In particular, the spatiotemporal dynamics of proteins that control key cellular processes such as transmission of the genetic information, cell growth and division remain largely unexplored. In this Perspective article, I highlight outstanding fundamental questions related to these aspects and arising from the original biology of this bacterium. I also discuss available insights and potential cell biology approaches based on quantitative live imaging techniques, in combination with Bacterial Genetics and biochemistry, to shed light on the intracellular organization of B. bacteriovorus in space and time.
Yoshiki Uchikawa - One of the best experts on this subject based on the ideXlab platform.
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fuzzy logic controllers generated by pseudo Bacterial genetic algorithm with adaptive operator
Proceedings of International Conference on Neural Networks (ICNN'97), 1997Co-Authors: N.e. Nawa, Tomonori Hashiyama, Takeshi Furuhashi, Yoshiki UchikawaAbstract:This paper presents a new genetic operator called adaptive operator to improve local portions of chromesomes. This new operator is implemented in a pseudo-Bacterial genetic algorithm (PBGA). The PBGA was proposed by the authors as a new approach combining a genetic algorithm (GA) with a local improvement mechanism inspired by a process in Bacterial Genetics. The PBGA was applied for the acquisition of fuzzy rules. The aim of the newly introduced adaptive operator is to improve the quality of the generated rules of the fuzzy models, producing blocks of effective rules and more compact models. The new operator adaptively decides the division points of each chromosome for the Bacterial mutation and the cutting points for the crossover, according to the distribution of degrees of truth values of the rules. In this paper, first, results obtained when using the PBGA with the adaptive operator for a simple fuzzy modeling problem are presented. Second, the PBGA with adaptive operator is used in the design of a fuzzy logic controller for a semi-active suspension system. The results show the benefits obtained with this operator.
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a study on fuzzy rules discovery using pseudo Bacterial genetic algorithm with adaptive operator
IEEE International Conference on Evolutionary Computation, 1997Co-Authors: N.e. Nawa, Tomonori Hashiyama, Takeshi Furuhashi, Yoshiki UchikawaAbstract:This paper presents a new operator called adaptive operator for the Pseudo-Bacterial Genetic Algorithm (PBGA). The PBGA was proposed by the authors as a new approach combining a genetic algorithm (GA) with a local improvement mechanism inspired by a process in Bacterial Genetics. The PBGA was applied for the discovery of fuzzy rules. The aim of the newly introduced adaptive operator is to improve the quality of the generated fuzzy rules, producing blocks of effective rules and more compact rule bases. The new operator adaptively decides the division points of each chromosome for the Bacterial mutation and the cutting points for the crossover. In order to verify the efficiency of the proposed adaptive operator, the PBGA is applied to a simple fuzzy modeling problem. The new operator actuates according to the distribution of degrees of truth values of the rules. The results show the benefits that can be obtained with this operator.
Kathryn Deriemer - One of the best experts on this subject based on the ideXlab platform.
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impact of Bacterial Genetics on the transmission of isoniazid resistant mycobacterium tuberculosis
PLOS Pathogens, 2006Co-Authors: Sebastien Gagneux, Marcos Burgos, Kathryn Deriemer, Antonio Enciso, Samira Munoz, Phillip C Hopewell, Peter M Small, Alexander S PymAbstract:Understanding the ecology of drug-resistant pathogens is essential for devising rational programs to preserve the effective lifespan of antimicrobial agents and to abrogate epidemics of drug-resistant organisms. Mathematical models predict that strain fitness is an important determinant of multidrug-resistant Mycobacterium tuberculosis transmission, but the effects of strain diversity have been largely overlooked. Here we compared the impact of resistance mutations on the transmission of isoniazid-resistant M. tuberculosis in San Francisco during a 9-y period. Strains with a KatG S315T or inhA promoter mutation were more likely to spread than strains with other mutations. The impact of these mutations on the transmission of isoniazid-resistant strains was comparable to the effect of other clinical determinants of transmission. Associations were apparent between specific drug resistance mutations and the main M. tuberculosis lineages. Our results show that in addition to host and environmental factors, strain genetic diversity can influence the transmission dynamics of drug-resistant bacteria.