title: Comparative Genomics of Field Isolates of Mycobacterium bovis and M. caprae Provides Evidence for Possible Correlates with Bacterial Viability and Virulence.
abstract: 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.
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain.|Department of Veterinary Pathobiology, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, Oklahoma, United States of America.
authors.forename: José
authors.initials: J
authors.lastname: de la Fuente
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain.|Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Iratxe
authors.initials: I
authors.lastname: Díez-Delgado
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Marinela
authors.initials: M
authors.lastname: Contreras
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Vicente
authors.affiliation: Center for Infection and Immunity of Lille (CIIL), INSERM U1019 -CNRS UMR 8204, Université de Lille, Institut Pasteur de Lille, Lille, France.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cabezas-Cruz
authors.affiliation: Oh no sequences! Research Group, Era7 Bioinformatics, Granada, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Tobes
authors.affiliation: Oh no sequences! Research Group, Era7 Bioinformatics, Granada, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Manrique
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Vladimir
authors.initials: V
authors.lastname: López
authors.affiliation: Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Romero
authors.affiliation: Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Universidad Complutense de Madrid, Madrid, Spain.|MAEVA SERVET S.L., Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Bezos
authors.affiliation: Centro de Vigilancia Sanitaria Veterinaria (VISAVET), Universidad Complutense de Madrid, Madrid, Spain.
authors.forename: Lucas
authors.initials: L
authors.lastname: Dominguez
authors.affiliation: NEIKER-Tecnalia, Instituto Vasco de Investigación y Desarrollo Agrario, Departamento de Sanidad Animal, Vizcaya, Spain.
authors.forename: Iker A
authors.initials: IA
authors.lastname: Sevilla
authors.affiliation: NEIKER-Tecnalia, Instituto Vasco de Investigación y Desarrollo Agrario, Departamento de Sanidad Animal, Vizcaya, Spain.
authors.forename: Joseba M
authors.initials: JM
authors.lastname: Garrido
authors.affiliation: NEIKER-Tecnalia, Instituto Vasco de Investigación y Desarrollo Agrario, Departamento de Sanidad Animal, Vizcaya, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Juste
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Madico
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: Edward
authors.initials: E
authors.lastname: Jones-López
authors.affiliation: SaBio, Instituto de Investigación en Recursos Cinegéticos IREC-CSIC-UCLM-JCCM, Ciudad Real, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Gortazar
mesh_terms: D000818:Animals; D019295:Computational Biology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D023281:Genomics; D006801:Humans; D050296:Microbial Viability; D009161:Mycobacterium / Q000235:genetics* / Q000302:isolation & purification*; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D004269:DNA, Bacterial; D037521:Virulence Factors