Genomewide overexpression screen for fosfomycin resistance in Escherichia coli: Mura confers clinical resistance at low fitness cost

To determine whether the overexpression of chromosomal genes can confer fosfomycin resistance, genomewide screening of a complete set of 5,272 plasmid-expressed open reading frames of Escherichia coli (ASKA collection) was performed. Major results are that (i) no clinical level of resistance is achieved by overexpressing chromosomal genes, except murA; (ii) this level is reached at a low fitness cost; and (iii) this cost is much lower than that imposed by other mutations conferring fosfomycin resistance.Ministerio de Ciencia e Innovación y Instituto de Salud Carlos III PI10/00105Spanish Network for Research on Infectious Diseases REIPI RD06/000

Comparación de las categorías clínicas de cepas de Escherichia coli que contienen definidos mecanismos cromosómicos y plasmídicos de resistencia a quinolonas según CLSI y EUCAST

[EN] EUCAST breakpoints are more restrictive than those defined by CLSI. This study highlights the discrepancies between CLSI and EUCAST in a well characterized isogenic Escherichia coli collection and their correlations with specific quinolone resistance mechanisms. The greatest number of discrepancies was observed in strains containing 2–4 resistance mechanisms (MIC values on the borderline of clinical resistance). Bearing in mind that quinolones are concentration dependent antimicrobial agents, small changes in MIC may have relevant consequences for treatment outcomes.[ES] Los puntos de corte de EUCAST son más restrictivos que los definidos por CLSI. Este estudio analiza las discrepancias entre CLSI y EUCAST en una colección isogénica de Escherichia coli y su correlación con mecanismos específicos de resistencia a quinolonas. El mayor número de discrepancias se observó en cepas que contienen 2–4 mecanismos de resistencia (con CMI en el límite de la resistencia clínica). Teniendo en cuenta que las quinolonas son agentes antimicrobianos concentración-dependientes, pequeños cambios en el valor de la CMI pueden tener consecuencias relevantes para el resultado del tratamiento.Peer reviewe

Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli

Bactericidal activity of quinolones has been related to a combination of DNA fragmentation, reactive oxygen species (ROS) production and programmed cell death (PCD) systems. The underlying molecular systems responsible for reducing bactericidal effect during antimicrobial therapy in low-level quinolone resistance (LLQR) phenotypes need to be clarified. To do this and also define possible new antimicrobial targets, the transcriptome profile of isogenic Escherichia coli harboring quinolone resistance mechanisms in the presence of a clinical relevant concentration of ciprofloxacin was evaluated. A marked differential response to ciprofloxacin of either up- or downregulation was observed in LLQR strains. Multiple genes implicated in ROS modulation (related to the TCA cycle, aerobic respiration and detoxification systems) were upregulated (sdhC up to 63.5-fold) in mutants with LLQR. SOS system components were downregulated (recA up to 30.7-fold). yihE, a protective kinase coding for PCD, was also upregulated (up to 5.2-fold). SdhC inhibition sensitized LLQR phenotypes (up to ΔLog = 2.3 after 24 h). At clinically relevant concentrations of ciprofloxacin, gene expression patterns in critical systems to bacterial survival and mutant development were significantly modified in LLQR phenotypes. Chemical inhibition of SdhC (succinate dehydrogenase) validated modulation of ROS as an interesting target for bacterial sensitization.This work was supported by the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (projects PI11-00934 and PI14/00940) and the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (P11-CTS-7730), Spain, by the Plan Nacional de I+D+i 2008–2011 and the Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, the Spanish Network for Research in Infectious Diseases (REIPI RD12/0015)—co-financed by European Development Regional Fund ‘A way to achieve Europe’ ERDF.Peer reviewe

Teachers' network and digital repository of educational resources: A history of contemporary capitalism I. The crisis of the liberal State and the first globalization through filmic, literary and aesthetic sources.

Se trata de crear un repositorio digital de apoyo a la docencia virtual, con contribuciones innovadoras en el empleo de fuentes artísticas y culturales para el estudio de la crisis del Estado liberal y de la primera globalización (1920-1930).This project aims to create a digital repository to support virtual teaching, with innovative contributions in the use of artistic and cultural sources for the study of the crisis of the liberal State and the first globalization (1920-1930).Depto. de Filosofía y SociedadFac. de FilosofíaFALSEUCMsubmitte