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Evolution and transmission of drug-resistant tuberculosis in a Russian population

Casali, Nicola ; Nikolayevskyy, Vladyslav ; Balabanova, Yanina ; Harris, Simon R ; Ignatyeva, Olga ; Kontsevaya, Irina ; Corander, Jukka ; Bryant, Josephine ; Parkhill, Julian ; Nejentsev, Sergey ; Horstmann, Rolf D ; Brown, Timothy ; Drobniewski, Francis

Nature genetics, 2014-03, Vol.46 (3), p.279-286 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Evolution and transmission of drug-resistant tuberculosis in a Russian population
Autor: Casali, Nicola ; Nikolayevskyy, Vladyslav ; Balabanova, Yanina ; Harris, Simon R ; Ignatyeva, Olga ; Kontsevaya, Irina ; Corander, Jukka ; Bryant, Josephine ; Parkhill, Julian ; Nejentsev, Sergey ; Horstmann, Rolf D ; Brown, Timothy ; Drobniewski, Francis
Assuntos: Antibiotics ; Bacterial Proteins - genetics ; Confidence intervals ; Disease transmission ; DNA-Directed RNA Polymerases ; Drug resistance ; Drug resistance in microorganisms ; Drug Resistance, Multiple, Bacterial - genetics ; Evolution, Molecular ; Extensively Drug-Resistant Tuberculosis - epidemiology ; Extensively Drug-Resistant Tuberculosis - microbiology ; Extensively Drug-Resistant Tuberculosis - transmission ; Genes, Bacterial ; Genetic aspects ; Genomes ; Humans ; Medical research ; Medicine, Experimental ; Mortality ; Mutation ; Mycobacterium ; Mycobacterium tuberculosis - drug effects ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - pathogenicity ; Patients ; Phylogeny ; Polymorphism, Single Nucleotide ; Prevalence ; Prospective Studies ; Public health ; Russia - epidemiology ; Software ; Tuberculosis ; Tuberculosis, Multidrug-Resistant - epidemiology ; Tuberculosis, Multidrug-Resistant - microbiology ; Tuberculosis, Multidrug-Resistant - transmission ; Virulence - genetics
É parte de: Nature genetics, 2014-03, Vol.46 (3), p.279-286
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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NC, VN, YB and FD designed the study; OI, IK, VN and YB recruited patients and collected epidemiological data; OI and IK performed laboratory work; NC, SRH and JC conducted sequence analysis; NC, TB, VN and FD interpreted the data; YB, OI and FD performed statistical comparisons; NC and FD drafted the paper; TB, VN, YB, OI, IK, SRH, JP, JB, SN, and RDH provided critical analysis and reviewed the manuscript. All authors approved the final draft.
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Descrição: The molecular mechanisms determining the transmissibility and prevalence of drug-resistant tuberculosis in a population were investigated through whole-genome sequencing of 1,000 prospectively obtained patient isolates from Russia. Two-thirds belonged to the Beijing lineage, which was dominated by two homogeneous clades. Multidrug-resistant (MDR) genotypes were found in 48% of isolates overall and in 87% of the major clades. The most common rpoB mutation was associated with fitness-compensatory mutations in rpoA or rpoC, and a new intragenic compensatory substitution was identified. The proportion of MDR cases with extensively drug-resistant (XDR) tuberculosis was 16% overall, with 65% of MDR isolates harboring eis mutations, selected by kanamycin therapy, which may drive the expansion of strains with enhanced virulence. The combination of drug resistance and compensatory mutations displayed by the major clades confers clinical resistance without compromising fitness and transmissibility, showing that, in addition to weaknesses in the tuberculosis control program, biological factors drive the persistence and spread of MDR and XDR tuberculosis in Russia and beyond.
Editor: United States: Nature Publishing Group
Idioma: Inglês

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Evolution and transmission of drug-resistant tuberculosis in a Russian population

Casali, Nicola ; Nikolayevskyy, Vladyslav ; Balabanova, Yanina ; Harris, Simon R ; Ignatyeva, Olga ; Kontsevaya, Irina ; Corander, Jukka ; Bryant, Josephine ; Parkhill, Julian ; Nejentsev, Sergey ; Horstmann, Rolf D ; Brown, Timothy ; Drobniewski, Francis

United States: Nature Publishing Group

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