Caracterización de nuevos factores de virulencia del patógeno nosocomial Acinetobacter baumannii

Programa Oficial de Doutoramento en Bioloxía Celular e Molecular . 5004V01[Resumo] Acinetobacter baumannii é un patóxeno oportunista que xurdiu nos últimos anos como un dos microorganismos máis perigosos dentro do ambiente hospitalario. Na presente tese doutoral caracterizáronse dous novos factores de virulencia que poderían explicar parcialmente a habilidade que ten A. baumannii para causar unha infección. O xene LH92_11085 de A. baumannii MAR002, implicado na formación dun pilus tipo chaperona- usher, atopouse sobreexpresado en células do biofilm en comparación con células planctónicas. A inactivación deste xene resultou nunha redución na capacidade da cepa de formar biofilm e de adherirse a células epiteliais e nun descenso na virulencia. O xene A1S_0242 (feoA) da cepa A. baumannii ATCC 17978, que está implicado na captación de ferro e que se atopou sobreexpresado durante un proceso de pneumonía, xoga un papel na adhesión, na formación de biofilm, na resistencia ó estrés oxidativo e na virulencia in vivo. Todos os resultados obtidos durante esta tese doutoral demostraron a contribución destes xenes na patoxénese de A. baumannii.[Resumen] Acinetobacter baumannii es un patógeno oportunista que ha emergido en los últimos años como uno de los microorganismos más peligrosos dentro del ambiente hospitalario. En la presente tesis doctoral se caracterizaron dos nuevos factores de virulencia que podrían explicar parcialmente la habilidad que tiene A. baumannii para causar una infección. El gen LH92_11085 de A. baumannii MAR002, implicado en la formación de un pilus tipo chaperona-usher, se encontró sobreexpresado en células del biofilm en comparación con células planctónicas. La inactivación de este gen resultó en una reducción en la capacidad de la cepa de formar biofilm y de adherirse a células epiteliales y un descenso en la virulencia. El gen A1S_0242 (feoA) de la cepa A. baumannii ATCC 17978, que está implicado en la captación de hierro y que se encontró sobreexpresado durante un proceso de neumonía, juega un papel en la adhesión, la formación de biofilm, la resistencia al estrés oxidativo y en la virulencia in vivo. Todos los resultados obtenidos durante esta tesis doctoral demostraron la contribución de estos genes a la patogénesis de A. baumannii.[Abstract] Acinetobacter baumannii is an opportunist pathogen that has emerged in the last years as one of the most dangerous microorganisms living in hospital environments. In the present work two new virulence factors, that could partially explain the ability of A. baumannii to cause an infection, have been characterized. The LH92_11085 gene of the A. baumannii MAR002 strain, involved in the formation of a chaperone-usher pilus system, was found as over-expressed in biofilm cells compared to planktonic cells. The inactivation of this gene resulted in a reduction in the capacity of the MAR002 strain to form biofilm and to adhere to human epithelial cells and in a decrease in virulence. The A1S_0242 gene (feoA) from the A. baumannii ATCC 17978 strain, which is involved in iron uptake and that was found as over-expressed during the course of a pneumonia infection, plays a role in adhesion, biofilm formation, resistance to oxidative stress and in virulence. Data obtained in this work demostrate the contribution of both genes to the pathogenesis of A. baumannii

Evolució i anàlisi del metabolisme ambiental del polígon industrial. El cas de Maó (Menorca)

El polígon industrial de Maó, POIMA, és un dels principals motors econòmics de l'illa de Menorca. La Universitat Autònoma de Barcelona (UAB) en col·laboració amb l'Observatori Socioambiental de Menorca (OBSAM), ha fet un projecte d'anàlisi de l'evolució històrica i del metabolisme actual del polígon. L'estudi es centra en 5 vectors; usos del sòl, energètic, hídric, materials i mobilitat dels quals les dades han estat obtingudes a partir d'enquestes, entrevistes a les empreses i observacions directes semi-quantitatives. Com a resultat es presenten diverses propostes de millora per augmentar l'eficiència de POIMA, analitzant el potencial d'autosuficiència energètic i hídric, reduint l'impacte ambiental i reutilitzant els residus com a recursos entre empreses, sinèrgies.The Mahon industrial park, POIMA, is the major economic driver of the island of Menorca. The university Autònoma de Barcelona (UAB) cooperating with the Observatori Socioambiental de Menorca (OBSAM) has a draft a project of analysis the history and the current metabolism of POIMA. The study is focused on five vectors, land use, energy, water, materials and mobility the data have been obtained through surveys, interviews to the companies and direct semi-quantitative observations. As a result, some proposal improvements have been designed in order to increase the efficiency of POIMA analyzing the potential of energy and water self-sufficiency, reducing environmental impact and reusing waste as resources between companies, called as a concept synergies

Involvement of HisF in the persistence of Acinetobacter baumannii during a pneumonia infection

[Abstract] Acinetobacter baumannii is currently considered one of themost problematic nosocomial microorganisms. In the present work the hisF gene from the ATCC 17978 strain and the AbH12O-A2 clinical isolate of A. baumannii was found over-expressed during the course of murine pneumonia infections. The study demonstrated that the A. baumannii ATCC 17978 mutant strain lacking the hisF gene induces a sub-lethal pneumonia infection in mice, while the complemented mutant strain increased its virulence. This histidine auxotroph mutant showed an increase on IL-6 secretion and leukocytes recruitment during infections. Furthermore, data revealed that the hisF gene, implicated in the innate immunity and inflammation, is involved in virulence during a pneumonia infection, which may partly explain the ability of this strain to persist in the lung. We suggest that HisF, essential for full virulence in this pathogen, should be considered a potential target for developing new antimicrobial therapies against A. baumannii.Instituto de Salud Carlos III; PI15/00860Instituto de Salud Carlos III; PI14/00059Instituto de Salud Carlos III; PI17/01482Axencia Galega de Innovación; IN607A 2016/22Spanish Network for Research in Infectious Diseases; REIPI RD12/0015/0014Spanish Network for Research in Infectious Diseases; REIPI RD16/0016/006Instituto de Salud Carlos III; FI18/00315Xunta de Galicia; IN606A-2019/029Xunta de Galicia; IN607A 2016/2

Optimización de Campus Virtual: archivo/repositorio en red de referencias artísticas desde 1900 hasta la actualidad

El objeto de este proyecto consiste en la realización de un espacio dentro del Campus Virtual de la UCM, que dote al estudiante de Bellas Artes de una herramienta digital de referencias artísticas desde el arte del siglo XX a nuestros días

In-Depth Analysis of the Role of the Acinetobactin Cluster in the Virulence of Acinetobacter baumannii

[Abstract] Acinetobacter baumannii is a multidrug-resistant pathogen that represents a serious threat to global health. A. baumannii possesses a wide range of virulence factors that contribute to the bacterial pathogenicity. Among them, the siderophore acinetobactin is one of the most important, being essential for the development of the infection. In this study we performed an in-depth analysis of the acinetobactin cluster in the strain A. baumannii ATCC 17978. For this purpose, nineteen individual isogenic mutant strains were generated, and further phenotypical analysis were performed. Individual mutants lacking the biosynthetic genes entA, basG, basC, basD, and basB showed a significant loss in virulence, due to the disruption in the acinetobactin production. Similarly, the gene bauA, coding for the acinetobactin receptor, was also found to be crucial for the bacterial pathogenesis. In addition, the analysis of the ΔbasJ/ΔfbsB double mutant strain demonstrated the high level of genetic redundancy between siderophores where the role of specific genes of the acinetobactin cluster can be fulfilled by their fimsbactin redundant genes. Overall, this study highlights the essential role of entA, basG, basC, basD, basB and bauA in the pathogenicity of A. baumannii and provides potential therapeutic targets for the design of new antivirulence agents against this microorganism.This work was funded by Projects PI15/00860 awarded to GB and PI17/01482 to AB and MP, all within in the National Plan for Scientific Research, Development and Technological Innovation 2013–2016 and funded by the ISCIII – General Subdirection of Assessment and Promotion of the Research-European Regional Development Fund (FEDER) “A way of making Europe.” The study was also funded by project IN607A 2016/22 (GAIN- Agencia Gallega de Innovación – Consellería de Economía, Emprego e Industria) awarded to GB. This work was also supported by Planes Nacionales de I + D + i 2008–2011/2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/006) co-financed by European Development Regional Fund “A way to achieve Europe” and operative program Intelligent Growth 2014–2020. This work was also supported by Grant RTI2018-093634-B-C22 (AEI/FEDER, EU) from the State Agency for Research (AEI) of Spain, co-funded by the FEDER Programme from the European Union and Xunta de Galicia for the support of Grant ED431E 2018/03 for CICA-INIBIC strategic and the initiative “Seed Projects 2019–2020.” JV-U was financially supported by the ISCIII project FI18/00315, LÁ-F by the ISCIII project PI14/00059 and the IN606B-2018/011, MM-G was financially supported by the Grant Clara Roy (SEIMC, Spanish Society of Clinical Microbiology and Infectious Diseases), KC-P by IN607A 2016/22 and AECC (Asociación Española Contra el Cáncer) predoctoral fellowship and LA by Xunta de Galicia co-funded with the European Social Fund (FSE) of the European Union (ED481A-2019/081)Xunta de Galicia; IN607A 2016/22Xunta de Galicia; ED431E 2018/03Xunta de Galicia; IN606B-2018/011Xunta de Galicia; IN607A 2016/22Xunta de Galicia; ED481A-2019/08

Contribution of the a-baumannii A1S_0114 gene to the interaction with eukaryotic cells and virulence

Genetic and functional studies showed that some components of the Acinetobacter baumannii ATCC 17978 A1S_0112-A1S_0119 gene cluster are critical for biofilm biogenesis and surface motility. Recently, our group has shown that the A1S_0114 gene was involved in biofilm formation, a process related with pathogenesis. Confirming our previous results, microscopy images revealed that the ATCC 17978 10114 derivative lacking this gene was unable to form a mature biofilm structure. Therefore, other bacterial phenotypes were analyzed to determine the role of this gene in the pathogenicity of A. baumannii ATCC 17978. The interaction of the ATCC 17978 parental strain and the 10114 mutant with A549 human alveolar epithelial cells was quantified revealing that the A1S_0114 gene was necessary for proper attachment to A549 cells. This dependency correlates with the negative effect of the A1S_0114 deletion on the expression of genes coding for surface proteins and pili-assembly systems, which are known to play a role in adhesion. Three different experimental animal models, including vertebrate and invertebrate hosts, confirmed the role of the A1S_0114 gene in virulence. All of the experimental infection assays indicated that the virulence of the ATCC 17978 was significantly reduced when this gene was inactivated. Finally, we discovered that the A1S_0114 gene was involved in the production of a small lipopeptide-like compound herein referred to as acinetin 505 (Ac-505). Ac-505 was isolated from ATCC 17978 spent media and its chemical structure was interpreted by mass spectrometry. Overall, our observations provide novel information on the role of the A1S_0114 gene in A. baumannii’s pathobiology and lay the foundation for future work to determine the mechanisms by which Ac-505, or possibly an Ac-505 precursor, could execute critical functions as a secondary metaboliteS

Optimización de Campus Virtual. Ampliación y ordenación del archivo/repositorio en red bajo el parámetro “estrategias artísticas"

Proyecto dedicado a ampliar e introducir un orden en la herramienta realizada en el Proyecto de Innovación y Mejora de la Calidad Docente, PIMCD nº 216, realizado durante el curso 2017-2018, y cuyo título fue: “Optimización de Campus Virtual: archivo/repositorio en red de referencias artísticas desde 1900 hasta la actualidad”. La ordenación se ha realizado mediante el parámetro "estrategias artísticas"

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality