Analysis of structural patterns in highly disaggregated bioeconomy sectors by EU Member States using SAM/IO multipliers

This report is part of a database and analytical work led by the Joint Research Centre (JRC.D.4, Seville) in cooperation with external experts to improve our understanding of job creation and economic growth in sectors related to the bioeconomy, with a focus on the agrifood sector.JRC.D.4-Economics of Agricultur

Low Ciprofloxacin concentrations select Multidrug-Resistant Mutants overproducing efflux pumps in clinical isolates of Pseudomonas Aeruginosa

Low antibiotic concentrations present in natural environments are a severe and often neglected threat to public health. Even if they are present below their MICs, they may select for antibiotic-resistant pathogens. Notably, the minimal subinhibitory concentrations that select resistant bacteria, and define the respective sub-MIC selective windows, differ between antibiotics. The establishment of these selective concentrations is needed for risk-assessment studies regarding the presence of antibiotics in different habitats. Using short-term evolution experiments in a set of 12 Pseudomonas aeruginosa clinical isolates (including high-risk clones with ubiquitous distribution), we have determined that ciprofloxacin sub-MIC selective windows are strain specific and resistome dependent. Nonetheless, in all cases, clinically relevant multidrug-resistant (MDR) mutants emerged upon exposure to low ciprofloxacin concentrations, with these concentrations being below the levels reported in ciprofloxacin-polluted natural habitats where P. aeruginosa can be present. This feature expands the conditions and habitats where clinically relevant quinolone-resistant mutants can emerge. In addition, we established the lowest concentration threshold beyond which P. aeruginosa, regardless of the strain, becomes resistant to ciprofloxacin. Three days of exposure under this sub-MIC "risk concentration" led to the selection of MDR mutants that displayed resistance mechanisms usually ascribed to high selective pressures, i.e., the overproduction of the efflux pumps MexCD-OprJ and MexEF-OprN. From a One-Health viewpoint, these data stress the transcendent role of low drug concentrations, which can be encountered in natural ecosystems, in aggravating the antibiotic resistance problem, especially when it comes to pathogens of environmental origin. IMPORTANCE It has been established that antibiotic concentrations below MICs can select antibiotic-resistant pathogens, a feature of relevance for analyzing the role of nonclinical ecosystems in antibiotic resistance evolution. The range of concentrations where this selection occurs defines the sub-MIC selective window, whose width depends on the antibiotic. Herein, we have determined the ciprofloxacin sub-MIC selective windows of a set of Pseudomonas aeruginosa clinical isolates (including high-risk clones with worldwide distribution) and established the lowest concentration threshold, notably an amount reported to be present in natural ecosystems, beyond which this pathogen acquires resistance. Importantly, our results show that this ciprofloxacin sub-MIC selects for multidrug-resistant mutants overproducing clinically relevant efflux pumps. From a One-Health angle, this information supports that low antimicrobial concentrations, present in natural environments, may have a relevant role in worsening the antibiotic resistance crisis, particularly regarding pathogens with environmental niches, such as P. aeruginosa. It has been established that antibiotic concentrations below MICs can select antibiotic-resistant pathogens, a feature of relevance for analyzing the role of nonclinical ecosystems in antibiotic resistance evolution. The range of concentrations where this selection occurs defines the sub-MIC selective window, whose width depends on the antibiotic

Centro Termal Balneario Paracuellos de Jiloca (Zaragoza): historia y generalidades

Se hace una reseña de la situación geográfica del Centro Termal Balneario Paracuellos de Jiloca, el más antiguo de Aragón, de los antecedentes históricos del mismo y situación actual. Se hace mención a sus propietarios, la composición química de sus aguas, así como a los datos referentes a la fecha de su apertura en 1847 y otros concernientes a la acción terapéutica de sus aguas

El Balneario de Villavieja (Castellón). Historia y generalidades

An account of the geographical position of Villavieja’s Spa is given, including a brief history of it and its situation nowdays. An particularly reference it is made about their propietaries and the first chemical composition of the mineral waters of this spa, the medical direction of the spa and the patients frequented the spa and another ones in relationship the medically effects of the waters and muthbath.  Se hace una reseña de la situación geográfica del Balneario de Villavieja, de los antecedentes históricos del mismo y situación actual. Se hace mención a sus propietarios, al primer análisis químico de las aguas mineromedicinales de este Balneario así como a los médicos directores, a los pacientes que lo han frecuentado y a las referencias a la acción terapéutica de sus aguas.

El balneario: historia y generalidades

An account of the geographical position of Villa Olmedo's Spa is given. Including a brief history of it and its situation nowadays. A particularly reference it is made about their proprietaries and the first chemical composition of the mineral medicinal waters of this spa and about the notices in relationship the date in which it was open (2006) and another ones in relationship the medically effects of the waters and muthbath. Se hace una reseña de la situación geográfica del Balneario de la Villa de Olmedo, de los antecedentes históricos del mismo y situación actual. Se hace mención a sus propietarios, al primer análisis químico de las aguas mineromedicinales de este Balneario así como a los datos referentes a la fecha de su apertura en 2006 y otros referentes a la acción terapéutica de sus aguas

Balneario de San Nicolás de Alhama (Almería). Historia y generalidades

Se hace una reseña de la situación geográfica del Balneario de San Nicolás, de los antecedentes históricos del mismo y situación actual así como de sus aguas minero-medicinales, sus propietarios, el primer análisis realizado por un farmacéutico, la dirección médica y los pacientes que le han frecuentado

Shifts in crane migration phenology associated with climate change in southwestern Europe

Gallocanta lagoon, NE Spain, is one of the main stopover and wintering areas of Common Cranes (Grus grus) migrating through Western Europe. We investigated how the water level of the lagoon where cranes roost, precipitation, and air temperature might have influenced the species’ migration and wintering patterns in this area between 1973 and 2018. Over the study period, the mean annual air temperature increased at 0.3 °C per decade. Simultaneously, cranes advanced the spring peak migration date at a rate of 0.37 days/year. Water level and rainfall during spring were also positively correlated with the date of spring migration peak. Because cranes need shallow water to roost, and must drink water from streams because the lagoon is saline, these correlations suggest that low water levels at roosting sites and drinking water shortage may have further accelerated the onset of northward spring migration. The water level was also positively correlated with peak crane numbers in autumn, suggesting that the roosting capacity of the lagoon may limit numbers of cranes that can stopover in the area. We conclude that global warming, variations in the water level of the lagoon, and precipitation during spring have determined changes in the use of Gallocanta as a staging and wintering area by Common Cranes during the last decades. Because climatic models predict further decreases in rainfall and higher temperatures in the area, further advances in the migration phenology of cranes should be expected, which might also have implications for the conservation and management of the species and the study area.project AgroSOS (CGL2015-66016-R Spanish Ministry of Economy and Competitiveness - FEDER funds [EU])Government of Aragón (Spain) through a predoctoral internship to J. M. Orellana (BOA 20/07/2017)Peer reviewe

Mutation Analysis in Regulator DNA-Binding Regions for Antimicrobial Efflux Pumps in 17,000 Pseudomonas aeruginosa Genomes

Mutations leading to upregulation of efflux pumps can produce multiple drug resistance in the pathogen Pseudomonas aeruginosa. Changes in their DNA binding regions, i.e., palindromic operators, can compromise pump depression and subsequently enhance resistance against several antibacterials and biocides. Here, we have identified (pseudo)palindromic repeats close to promoters of genes encoding 13 core drug-efflux pumps of P. aeruginosa. This framework was applied to detect mutations in these repeats in 17,292 genomes. Eighty-nine percent of isolates carried at least one mutation. Eight binary genetic properties potentially related to expression were calculated for mutations. These included palindromicity reduction, mutation type, positioning within the repeat and DNA-bending shift. High-risk ST298, ST308 and ST357 clones commonly carried four conserved mutations while ST175 and the cystic fibrosis-linked ST649 clones showed none. Remarkably, a T-to-C transition in the fourth position of the upstream repeat for mexEF-oprN was nearly exclusive of the high-risk ST111 clone. Other mutations were associated with high-risk sublineages using sample geotemporal metadata. Moreover, 1.5% of isolates carried five or more mutations suggesting they undergo an alternative program for regulation of their effluxome. Overall, P. aeruginosa shows a wide range of operator mutations with a potential effect on efflux pump expression and antibiotic resistance.This research was funded by Acción Estratégica en Salud from the ISCIII, grant MPY 509/19. This research was also supported by Personalized and Precision Medicine grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU.S

Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis

COVID-19; SARS-CoV-2; Electronic health recordsCOVID-19; SARS-CoV-2; Registros médicos electrónicosCOVID 19; SARS-CoV-2; Registres mèdics electrònicsBackground Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p < 0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062). Interpretation While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance.This work was supported by MSD and by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU through grants PI21/00017 and Personalized and precision medicine grant (MePRAM Project, PMP22/00092)