RT Journal Article
T1 Comparative Genomics of Field Isolates of Mycobacterium bovis and M. caprae Provides Evidence for Possible Correlates with Bacterial Viability and Virulence
A1 de la Fuente, José
A1 Díez Delgado, Iratxe
A1 Contreras, Marinela
A1 Vicente, Joaquín
A1 Cabezas Cruz, Alejandro
A1 Tobes, Raquel
A1 Manrique, Marina
A1 López, Vladimir
A1 Romero Martínez, Beatriz
A1 Bezos Garrido, Javier
A1 Sevilla, Iker A
A1 Garrido, Joseba M
A1 Juste, Ramón
A1 Madico, Guillermo
A1 Jones-López, Edward
A1 Gortazar, Christian
A1 Domínguez Rodríguez, Lucas José
AB 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.
PB Public Library Science
SN 1935-2735
YR 2015
FD 2015-11
LK https://hdl.handle.net/20.500.14352/24662
UL https://hdl.handle.net/20.500.14352/24662
LA eng
NO Unión Europea. FP7
NO Unión Europea. H2020
NO Ministerio de Economía y Competitividad (MINECO)
DS Docta Complutense
RD 30 abr 2024