title: Comparative genomic analysis of Mycobacterium tuberculosis drug resistant strains from Russia.
abstract: Tuberculosis caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (MTB) strains is a growing problem in many countries. The availability of the complete nucleotide sequences of several MTB genomes allows to use the comparative genomics as a tool to study the relationships of strains and differences in their evolutionary history including acquisition of drug-resistance. In our work, we sequenced three genomes of Russian MTB strains of different phenotypes--drug susceptible, MDR and XDR. Of them, MDR and XDR strains were collected in Tomsk (Siberia, Russia) during the local TB outbreak in 1998-1999 and belonged to rare KQ and KY families in accordance with IS6110 typing, which are considered endemic for Russia. Based on phylogenetic analysis, our isolates belonged to different genetic families, Beijing, Ural and LAM, which made the direct comparison of their genomes impossible. For this reason we performed their comparison in the broader context of all M. tuberculosis genomes available in GenBank. The list of unique individual non-synonymous SNPs for each sequenced isolate was formed by comparison with all SNPs detected within the same phylogenetic group. For further functional analysis, all proteins with unique SNPs were ascribed to 20 different functional classes based on Clusters of Orthologous Groups (COG). We have confirmed drug resistant status of our isolates that harbored almost all known drug-resistance associated mutations. Unique SNPs of an XDR isolate CTRI-4(XDR), belonging to a Beijing family were compared in more detail with SNPs of additional 14 Russian XDR strains of the same family. Only type specific mutations in genes of repair, replication and recombination system (COG category L) were found common within this group. Probably the other unique SNPs discovered in CTRI-4(XDR) may have an important role in adaptation of this microorganism to its surrounding and in escape from antituberculosis drugs treatment.
authors: Research Institute of Physical-Chemical Medicine, Moscow, Russian Federation.
authors: Elena N
authors: EN
authors: Ilina
authors: Egor A
authors: EA
authors: Shitikov
authors: Larisa N
authors: LN
authors: Ikryannikova
authors: Dmitry G
authors: DG
authors: Alekseev
authors: Dmitri E
authors: DE
authors: Kamashev
authors: Maja V
authors: MV
authors: Malakhova
authors: Tatjana V
authors: TV
authors: Parfenova
authors: Maxim V
authors: MV
authors: Afanas'ev
authors: Dmitry S
authors: DS
authors: Ischenko
authors: Nikolai A
authors: NA
authors: Bazaleev
authors: Tatjana G
authors: TG
authors: Smirnova
authors: Elena E
authors: EE
authors: Larionova
authors: Larisa N
authors: LN
authors: Chernousova
authors: Alexey V
authors: AV
authors: Beletsky
authors: Andrei V
authors: AV
authors: Mardanov
authors: Nikolai V
authors: NV
authors: Ravin
authors: Konstantin G
authors: KG
authors: Skryabin
authors: Vadim M
authors: VM
authors: Govorun
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D055028:Comparative Genomic Hybridization; D004269:DNA, Bacterial; D054908:Extensively Drug-Resistant Tuberculosis / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology*; D016680:Genome, Bacterial / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D010802:Phylogeny; D012426:Russia; D012800:Siberia
chemical_list: D000995:Antitubercular Agents; D004269:DNA, Bacterial