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

Investigation published in PLoS Neglected Tropical Diseases

November 19th, 2015

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




de la Fuente J., Diez-Delgado I., Contreras M., Vicente J., Cabezas-Cruz A., Tobes R., Manrique M., Lopez V., Romero B., Bezos J., Dominguez L., Sevilla I., Garrido JM., Juste R., Madico G., Jones-Lopez E. and Gortazar C.




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

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



Participants:

Gobierno de Castilla-La ManchaSanidad y Biotecnología (SaBio). Instituto de Investigación en Recursos Cinegéticos (IREC). Consejo Superior de Investigaciones Científicas (CSIC). Universidad de Castilla La Mancha (UCLM). Gobierno de Castilla-La Mancha (JCCM).

Oklahoma State UniversityDepartament of Veterinary Pathobiology. Center for Veterinary Health Sciences (CVHS). Oklahoma State University (OSU).

Universidad ComplutenseDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).

Université de Lille.

Institut Pasteur de LilleInstitut Pasteur de Lille.

Center for Infection and Immunity of Lille (CIIL).

Era 7 BioinformaticsEra 7 Bioinformatics.

Universidad ComplutenseServicio de Micobacterias (MYC). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

MAEVA SERVET, S.L.MAEVA SERVET, S.L..

Gobierno VascoInstituto Vasco de Investigación y Desarrollo Agrario (NEIKER). Gobierno Vasco.

Section of Infectious Diseases. Department of Medicine. Boston University School of Medicine (BUSM).







PLoS Neglected Tropical Diseases
FACTOR YEAR Q
3.948 2015

NLMID: 101291488

PMID: 26583774

ISSN: 1935-2735



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


JOURNAL: Plos Neglect Trop Dis


NUMERACIÓN: 9(11):e0004232


AÑO: 2015


PUBLISHER: PLOS


AUTHORS: de la Fuente J., Diez-Delgado I., Contreras M., Vicente J., Cabezas-Cruz A., Tobes R., Manrique M., Lopez V., Romero B., Bezos J., Dominguez L., Sevilla I., Garrido JM., Juste R., Madico G., Jones-Lopez E. and Gortazar C.


First
José de Jesús de la Fuente García
9th
Beatriz Romero Martínez
10
Javier Bezos Garrido
11th
Lucas Domínguez Rodríguez
Last
Christian Gortazar Schmidt

DOI: https://doi.org/10.1371/journal.pntd.0004232


CITE THIS PUBLICATION:

de la Fuente J., Diez-Delgado I., Contreras M., Vicente J., Cabezas-Cruz A., Tobes R., Manrique M., Lopez V., Romero B., Bezos J., Dominguez L., Sevilla I., Garrido JM., Juste R., Madico G., Jones-Lopez E. and Gortazar C. Comparative Genomics of Field Isolates of Mycobacterium bovis and M. caprae Provides Evidence for Possible Correlates with Bacterial Viability and Virulence. PLoS Neglected Tropical Diseases. 9(11):e0004232. 2015. (A). ISSN: 1935-2735. DOI: 10.1371/journal.pntd.0004232


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