68,653 research outputs found

    Global burden of colistin-resistant bacteria : mobilized colistin resistance genes study (1980-2018)

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    Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of mcr genes, their reservoirs and the potential pathways for human transmission are required to implement control and prevention strategies, yet such data are lacking. Publications from four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases published between 18 November 2015 and 30 December 2018 were identified. In this systematic review and meta-analysis, the prevalence of mcr genes in bacteria isolated from humans, animals, the environment and food products were investigated. A total of 974 publications were identified. 202 observational studies were included in the systematic review and 71 in the meta-analysis. mcr genes were reported from 47 countries across six continents and the overall average prevalence was 4.7% (0.1-9.3%). China reported the highest number of mcr-positive strains. Pathogenic Escherichia coli (54%), isolated from animals (52%) and harboring an IncI2 plasmid (34%) were the bacteria with highest prevalence of mcr genes. The estimated prevalence of mcr-1 pathogenic E. coli was higher in food-animals than in humans and food products, which suggests a role for foodborne transmission. This study provides a comprehensive assessment of prevalence of the mcr gene by source, organism, genotype and type of plasmid

    Insights into the Ecological Roles and Evolution of Methyl-Coenzyme M Reductase-Containing Hot Spring Archaea

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    Several recent studies have shown the presence of genes for the key enzyme associated with archaeal methane/alkane metabolism, methyl-coenzyme M reductase (Mcr), in metagenome-assembled genomes (MAGs) divergent to existing archaeal lineages. Here, we study the mcr-containing archaeal MAGs from several hot springs, which reveal further expansion in the diversity of archaeal organisms performing methane/alkane metabolism. Significantly, an MAG basal to organisms from the phylum Thaumarchaeota that contains mcr genes, but not those for ammonia oxidation or aerobic metabolism, is identified. Together, our phylogenetic analyses and ancestral state reconstructions suggest a mostly vertical evolution of mcrABG genes among methanogens and methanotrophs, along with frequent horizontal gene transfer of mcr genes between alkanotrophs. Analysis of all mcr-containing archaeal MAGs/genomes suggests a hydrothermal origin for these microorganisms based on optimal growth temperature predictions. These results also suggest methane/alkane oxidation or methanogenesis at high temperature likely existed in a common archaeal ancestor

    Escenario actual de la resistencia a la colistina mediada por plásmidos en América Latina

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    Colistin resistance can occur by chromosomal mutations and by acquisition of plasmid-carrying determinants, mainly mcr-1. In the recent years, we have observed the outburst of this resistance gene in our region. Due to the risk of the rapid dissemination of mcr-1, this finding has worried and alerted different actors from the health field and has become one of the most prolific topics. Our review compiles available reports of well-documented mcr-1-positive strains of Enterobacteriaceae, obtained from different samples in Argentina and other countries of Latin America. Furthermore, it addresses the association of mcr-1 with ESBL resistance markers and outlines the platforms involved in their dissemination.Fil: Quiroga, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Nastro, Marcela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Di Conza, José Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

    Molecular insights into functional differences between mcr-3- and mcr-1-mediated colistin resistance

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    The global emergence of plasmid-mediated colistin resistance genes mcr-1 and mcr-3 has threatened the role of the “last resort” drug colistin in the defense against infections caused by multidrug-resistant Gram-negative bacteria. However, functional differences between these two genes in mediating colistin resistance remains poorly understood. Protein sequence alignment of MCR-3 and MCR-1 was therefore conducted in Clustal Omega to identify sequence divergence. The molecular recognition of lipid A head group phosphatidylethanolamine and MCR-3 enzyme was studied by homology modeling and molecular docking, with the catalytic mechanism of MCR-3 also being explored. Thr277 in MCR-3 was validated as the key amino acid residue responsible for the catalytic reaction using site-directed mutagenesis and was shown to act as a nucleophile. Lipid A modification induced by the MCR-3 and MCR-1 enzymes was confirmed by electrospray ionization time-of-flight mass spectrometry. Far-UV circular dichroism spectra of the MCR-3 and MCR-1 enzymes suggested that MCR-3 was more thermostable than MCR-1, with a melting temperature of 66.19°C compared with 61.14°C for MCR-1. These data provided molecular insight into the functional differences between mcr-3 and mcr-1 in conferring colistin resistance

    The Mega-City-Region of Munich: A Kingdom of Its Own Or a Space of Inter-Connected Flows?

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    In a world of continuing globalization mega-city regions (MCR) are of increasing importance. MCR are defined by a high concentration of regulation, innovation and gateway functions. Planners and politicians alike recognise that competition on this new spatial scale is becoming a strategic tool to develop the whole country. So they are looking for spatial strategies to ensure economic success and sustainable development (social and spatial cohesion) at the same time. However, only little is known about the factors, which constitute MCRs, the inter-relationships within and between MCR, the primacy of individual functional urban areas within MCR and the potential methods to communicate these complex structures to politicians and stakeholders. The paper will deal with the following questions that will be tested with a case-study in the Munich metropolitan region, the so-called Greater Munich Area: (1) Which flows and inter-relationsships of knowledge based economic activities define the MCR? How is the MCR itself embedded in the global network of mega-city regions? (2) What spatial mismatch becomes recognisable when differentiating between functional and morphological polycentricity? (3) What functional polycentricity do firms in the Advanced Producer Services and in the High-Tech sectors produce when looking at their office location strategies? (4)What policy recommendations follow for sustainable spatial development? Our hypothesis is that the current perception of MCRs by local and regional stakeholders is quite inhomogeneous. There is an obvious gap between the functional logic of the competitive world and the territorial logic of the planning administrations. So we propose to look at the individual logics and the spatial reach of the stakeholders’ activites. The study will use an empirical survey for the Greater Munich Area that is mainly based on commuter data, location data of firms, business communication data and interviews with firms and a selection of key stakeholders.

    Multiplex PCR for detection of plasmid-mediated colistin resistance determinants, mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 for surveillance purposes

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    International audiencePlasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (mcr-1 to mcr-5, and variants) in Enterobacteriaceae was developed for surveillance or research purposes. Methods: We designed four new primer pairs to amplify mcr-1, mcr-2, mcr-3 and mcr-4 gene products and used the originally described primers for mcr-5 to obtain a stepwise separation of ca 200 bp between amplicons. The primer pairs and amplification conditions allow for single or multiple detection of all currently described mcr genes and their variants present in Enterobacteriaceae. The protocol was validated testing 49 European Escherichia coli and Salmonella isolates of animal origin. Results: Multiplex PCR results in bovine and porcine isolates from Spain, Germany, France and Italy showed full concordance with whole genome sequence data. The method was able to detect mcr-1, mcr-3 and mcr-4 as singletons or in different combinations as they were present in the test isolates. One new mcr-4 variant, mcr-4.3, was also identified. Conclusions: This method allows rapid identification of mcr-positive bacteria and overcomes the challenges of phenotypic detection of colistin resistance. The multiplex PCR should be particularly interesting in settings or laboratories with limited resources for performing genetic analysis as it provides information on the mechanism of colistin resistance without requiring genome sequencing

    Identification and characterization of mcr mediated colistin resistance in extraintestinal Escherichia coli from poultry and livestock in China

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    Antimicrobial resistance to colistin has emerged worldwide threatening the efficacy of one of the last-resort antimicrobials used for the treatment of multidrug-resistant Enterobacteriaceae infection in humans. In this study, we investigated the presence of colistin resistance genes (mcr-1, mcr-2, mcr-3) in Escherichia coli strains isolated from poultry and livestock collected between 2004 and 2012 in China. Furthermore, we studied the maintenance and transfer of the mcr-1 gene in E. coli after serial passages. Overall, 2.7% (17/624) of the E. coli isolates were positive for the mcr-1 gene while none were positive for the mcr-2 and mcr-3 genes. The prevalences of mcr-1 were similar in E. coli isolates from chickens (3.2%; 13/404), pigs (0.9%; 1/113) and ducks (6.8%; 3/44) but were absent in isolates from cattle (0/63). The mcr-1 gene was maintained in the E. coli after six passages (equivalent to 60 generations). In vitro transfer of mcr-1 was evident even without colistin selection. Our data indicate the presence of mcr-1 in extraintestinal E. coli from food-producing animals in China, and suggest that high numbers of the mcr-1-positive bacteria in poultry and livestock do not appear to be readily lost after withdrawal of colistin as a food additive

    Selection and validation of potato candidate genes for maturity corrected resistance to Phytophthora infestans based on differential expression combined with SNP association and linkage mapping.

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    Late blight of potato (Solanum tuberosum L.) caused by the oomycete Phytophthora infestans (Mont.) de Bary, is one of the most important bottlenecks of potato production worldwide. Cultivars with high levels of durable, race unspecific, quantitative resistance are part of a solution to this problem. However, breeding for quantitative resistance is hampered by the correlation between resistance and late plant maturity, which is an undesirable agricultural attribute. The objectives of our research are (i) the identification of genes that condition quantitative resistance to P. infestans not compromised by late plant maturity and (ii) the discovery of diagnostic single nucleotide polymorphism (SNP) markers to be used as molecular tools to increase efficiency and precision of resistance breeding. Twenty two novel candidate genes were selected based on comparative transcript profiling by SuperSAGE (serial analysis of gene expression) in groups of plants with contrasting levels of maturity corrected resistance (MCR). Reproducibility of differential expression was tested by quantitative real time PCR and allele specific pyrosequencing in four new sets of genotype pools with contrasting late blight resistance levels, at three infection time points and in three independent infection experiments. Reproducibility of expression patterns ranged from 28 to 97%. Association mapping in a panel of 184 tetraploid cultivars identified SNPs in five candidate genes that were associated with MCR. These SNPs can be used in marker-assisted resistance breeding. Linkage mapping in two half-sib families (n = 111) identified SNPs in three candidate genes that were linked with MCR. The differentially expressed genes that showed association and/or linkage with MCR putatively function in phytosterol synthesis, fatty acid synthesis, asparagine synthesis, chlorophyll synthesis, cell wall modification, and in the response to pathogen elicitors
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