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

Abstract

Ancient 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.

Phylogenetic relationships of Mycobacterium tuberculosis isolates in Poland: The emergence of Beijing genotype among multidrug-resistant cases

“…Interestingly, the XDR isolates of SIT266 (LAM family), highly-prevalent in Belarus, were not found in this study ( Zalutskaya et al., 2013 ). This SIT remains also at a low prevalence in Russia ( Mokrousov et al., 2021 ). This might be largely explained by the lack of mass migration from Belarus to Russia and to Poland.…”

“…Of note, one patient born in Poland was infected with type MLVA 1071-32, which has been recently described as an emerging resistant Beijing variant that is circulating in Siberia. This variant has been rarely found in the European part of Russia and only sporadically in Balkan countries ( Mokrousov et al., 2021 ).…”

Genetic Diversity and Primary Drug Resistance of Mycobacterium tuberculosis Beijing Genotype Strains in Northwestern Russia

“…In that database, M41 is a minor variant that was detected >10 years ago in single isolates in the earlier studies in Northwestern Russia (Pskov, Kaliningrad, St. Petersburg) and was also described in Lithuania (4 drug-susceptible out of 157 Beijing isolates [ 2 ]). Finally, MDR/pre-XDR type 1071-32 belongs to the early ancient Beijing sublineage, recently discovered in Western Siberia at 10% and endemic to Russia; its secondary single isolates were described in parts of the Former Soviet Union and Eastern Europe [ 47 ].…”

Genetic diversity, evolution and drug resistance of Mycobacterium tuberculosis lineage 2

“…Initially, two insertions were found: at the dnaA-dnaN origin of replication of the M. tuberculosis chromosome and one or two IS6110 insertions (two for the W strain) in the NTF region (Bifani et al, 2002). Currently, IS6110-RFLP typing is not as common as before, however, IS6110-RFLP profiles have been accumulated in various databases (RIVM in the Netherlands), or PHRI in the USA and can be used to track strains in historical collections, which is compatible with more modern methods such as WGS (Mokrousov et al, 2021). However, the specific insertion site of this element in the Rv2180c gene is used to identify the Beijing family using PCR among clinical strains (Pérez-Lago et al, 2019).…”