title: In-depth analysis of the genome sequence of a clinical, extensively drug-resistant Mycobacterium bovis strain.
abstract: Although human-to-human transmission of Mycobacterium bovis strains and other members of the animal lineage of the tubercle bacilli is a rare event, an extensively drug resistant (XDR) strain, named M. bovis B strain, caused a lethal outbreak in the nineties in Spain. The genome of M. bovis B strain was re-sequenced by SOLiD platform and mapped to the reference M. bovis AF2122/97. The genetic polymorphisms detected have been analysed in depth. One hundred and fifty-eight specific non-synonymous SNPs were detected; ninety-two of these were non-conservative. In addition, one specific 3195-bp insertion could be identified as an ABC transporter gene by homology with tbd2 gene, which was found to be present in other clinical M. bovis strains. Its peculiar phenotype profile of resistance was explained by molecular characteristics, including a 5685-bp specific deletion that revealed a novel polymorphism associated with resistance to paraminosalicilic acid. From a phylogenetical point of view, according to the SNPs detected, M. bovis B could be included into the clonal complex M. bovis European 2. This is the first time that a deep analysis of the whole-genome sequencing of an extensively drug-resistant M. bovis strain is detailed. It offers the explanation for the resistance and found several data to be incorporated for future research.
authors.affiliation: IIS Aragón/Instituto Aragonés de Ciencias de la Salud, Spain. Electronic address: sarasagasti@hotmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Sagasti
authors.affiliation: IIS Aragón/Hospital Universitario Miguel Servet, Spain. Electronic address: isiml68@gmail.com.
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Millán-Lou
authors.affiliation: Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain. Electronic address: msjimenz@isciii.es.
authors.forename: María
authors.initials: M
authors.lastname: Soledad Jiménez
authors.affiliation: IIS Aragón/Hospital Universitario Miguel Servet, Spain; Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain; CIBER de Enfermedades Respiratorias, Zaragoza, Spain. Electronic address: carlos@unizar.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Martín
authors.affiliation: IIS Aragón/Instituto Aragonés de Ciencias de la Salud, Spain; IIS Aragón/Hospital Universitario Miguel Servet, Spain; CIBER de Enfermedades Respiratorias, Zaragoza, Spain. Electronic address: ssamper.iacs@aragon.es.
authors.forename: Sofía
authors.initials: S
authors.lastname: Samper
mesh_terms: D004269:DNA, Bacterial / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D017353:Gene Deletion; D016678:Genome; D006801:Humans; D016254:Mutagenesis, Insertional; D009163:Mycobacterium bovis / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods; D014376:Tuberculosis / Q000382:microbiology*; D014774:Virulence / Q000235:genetics
chemical_list: D004269:DNA, Bacterial
keywords: Mycobacterium bovis B; Outbreak; XDR-resistance