Comparative Genomics of Field Isolates of Mycobacterium bovis and M. caprae Provides Evidence for Possible Correlates with Bacterial Viability and Virulence

Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly affect humans and animals worldwide. The life cycle of mycobacteria is complex and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Recently, comparative genomics analyses have provided new insights into the evolution and adaptation of the MTBC to survive inside the host. However, most of this information has been obtained using M. tuberculosis but not other members of the MTBC such as M. bovis and M. caprae. In this study, the genome of three M. bovis (MB1, MB3, MB4) and one M. caprae (MB2) field isolates with different lesion score, prevalence and host distribution phenotypes were sequenced. Genome sequence information was used for whole-genome and protein-targeted comparative genomics analysis with the aim of finding correlates with phenotypic variation with potential implications for tuberculosis (TB) disease risk assessment and control. At the whole-genome level the results of the first comparative genomics study of field isolates of M. bovis including M. caprae showed that as previously reported for M. tuberculosis, sequential chromosomal nucleotide substitutions were the main driver of the M. bovis genome evolution. The phylogenetic analysis provided a strong support for the M. bovis/M. caprae clade, but supported M. caprae as a separate species. The comparison of the MB1 and MB4 isolates revealed differences in genome sequence, including gene families that are important for bacterial infection and transmission, thus highlighting differences with functional implications between isolates otherwise classified with the same spoligotype. Strategic protein-targeted analysis using the ESX or type VII secretion system, proteins linking stress response with lipid metabolism, host T cell epitopes of mycobacteria, antigens and peptidoglycan assembly protein identified new genetic markers and candidate vaccine antigens that warrant further study to develop tools to evaluate risks for TB disease caused by M. bovis/M.caprae and for TB control in humans and animals.

Avel·lí Artís i Balaguer (1881-1954), comediógrafo e impresor-editor. Entre la plenitud del cambio de siglos y el exilio

This thesis has its origin in a previous work: “The Catalan theatrical life in the magazine ‘El Teatre Català’ (1912-1917)” (DEA, UCM, 2004-2005), focused on the history, description and the indexes of that magazine. Among the historical and literary references ordered there, we chose a figure that would make a monographic work resulting in the present Doctoral Thesis. The choice fell on Avel·lí Artís i Balaguer (1881-1954), whose personality and literary corpus, allow additional possibilities for research. The cultural and literary reach of his life and his work covers a whole historical cycle in Catalan culture and literature, which moves from its contemporary consolidation towards the drama of its temporal dislocation, between the Spanish Civil War and the exile experience. This e historical itinerary is represented by Avel·lí Artís i Balaguer, being a playwright and a publisher. He’s been considered a comedy playwright since his editions bear titles such as “comedy”, “pas comedy”, “sainet” “quadro”, “farce” or “dialogue”, at most we find the word “Drama” once and “tragicomedy” twice, and we can find all this, in a series of texts for the representation ranging from 1909 to 1938. Secondly, as a professional fully involved in printing and publishing, thereby covering since its first steps as a compositor in the late nineties of the 19th century until his activity as a crucial character for magazines and other publishing projects, from the first decade of the 20th century until the last year of his Mexican exile...