Practical approach to detection and surveillance of emerging highly resistant Mycobacterium tuberculosis Beijing 1071-32-cluster

Author:

Mokrousov Igor,Vyazovaya Anna,Sinkov Viacheslav,Gerasimova Alena,Ioannidis Panayotis,Jiao Weiwei,Khromova Polina,Papaventsis Dimitrios,Pasechnik Oksana,Perdigão João,Rastogi Nalin,Shen Adong,Skiba Yuriy,Solovieva Natalia,Suffys Philip,Tafaj Silva,Umpeleva Tatiana,Vakhrusheva Diana,Yarusova Irina,Zhdanova Svetlana,Zhuravlev Viacheslav,Ogarkov Oleg

Abstract

AbstractAncient sublineage of the Mycobacterium tuberculosis Beijing genotype is endemic and prevalent in East Asia and rare in other world regions. While these strains are mainly drug susceptible, we recently identified a novel clonal group Beijing 1071-32 within this sublineage emerging in Siberia, Russia and present in other Russian regions. This cluster included only multi/extensive drug resistant (MDR/XDR) isolates. Based on the phylogenetic analysis of the available WGS data, we identified three synonymous SNPs in the genes Rv0144, Rv0373c, and Rv0334 that were specific for the Beijing 1071-32-cluster and developed a real-time PCR assay for their detection. Analysis of the 2375 genetically diverse M. tuberculosis isolates collected between 1996 and 2020 in different locations (European and Asian parts of Russia, former Soviet Union countries, Albania, Greece, China, Vietnam, Japan and Brazil), confirmed 100% specificity and sensitivity of this real-time PCR assay. Moreover, the epidemiological importance of this strain and the newly developed screening assay is further stressed by the fact that all identified Beijing 1071-32 isolates were found to exhibit MDR genotypic profiles with concomitant resistance to additional first-line drugs due to a characteristic signature of six mutations in rpoB450, rpoC485, katG315, katG335, rpsL43 and embB497. In conclusion, this study provides a set of three concordant SNPs for the detection and screening of Beijing 1071-32 isolates along with a validated real-time PCR assay easily deployable across multiple settings for the epidemiological tracking of this significant MDR cluster.

Funder

Russian Science Foundation

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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