title: Mycobacterium tuberculosis Type II Toxin-Antitoxin Systems: Genetic Polymorphisms and Functional Properties and the Possibility of Their Use for Genotyping.
abstract: Various genetic markers such as IS-elements, DR-elements, variable number tandem repeats (VNTR), single nucleotide polymorphisms (SNPs) in housekeeping genes and other groups of genes are being used for genotyping. We propose a different approach. We suggest the type II toxin-antitoxin (TA) systems, which play a significant role in the formation of pathogenicity, tolerance and persistence phenotypes, and thus in the survival of Mycobacterium tuberculosis in the host organism at various developmental stages (colonization, infection of macrophages, etc.), as the marker genes. Most genes of TA systems function together, forming a single network: an antitoxin from one pair may interact with toxins from other pairs and even from other families. In this work a bioinformatics analysis of genes of the type II TA systems from 173 sequenced genomes of M. tuberculosis was performed. A number of genes of type II TA systems were found to carry SNPs that correlate with specific genotypes. We propose a minimally sufficient set of genes of TA systems for separation of M. tuberculosis strains at nine basic genotype and for further division into subtypes. Using this set of genes, we genotyped a collection consisting of 62 clinical isolates of M. tuberculosis. The possibility of using our set of genes for genotyping using PCR is also demonstrated.
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.|Scientific Research Center for Biotechnology of Antibiotics "BIOAN", Moscow, Russia.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Zaychikova
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Zakharevich
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.|State University, Moscow Institute of Physics and Technology, Moscow, Russia.
authors.forename: Maria O
authors.initials: MO
authors.lastname: Sagaidak
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Nadezhda A
authors.initials: NA
authors.lastname: Bogolubova
authors.affiliation: Central Research Institute of Tuberculosis, Moscow, Russia.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Smirnova
authors.affiliation: Central Research Institute of Tuberculosis, Moscow, Russia.
authors.forename: Sofya N
authors.initials: SN
authors.lastname: Andreevskaya
authors.affiliation: Central Research Institute of Tuberculosis, Moscow, Russia.
authors.forename: Elena E
authors.initials: EE
authors.lastname: Larionova
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Alekseeva
authors.affiliation: Central Research Institute of Tuberculosis, Moscow, Russia.
authors.forename: Larisa N
authors.initials: LN
authors.lastname: Chernousova
authors.affiliation: Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia.|Scientific Research Center for Biotechnology of Antibiotics "BIOAN", Moscow, Russia.
authors.forename: Valery N
authors.initials: VN
authors.lastname: Danilenko
mesh_terms: D000992:Antitoxins / Q000235:genetics* / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D016680:Genome, Bacterial; D060005:Genotyping Techniques / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins