In vivo virulence of Beijing genotype Mycobacterium tuberculosis

Abstract

Mycobacterium tuberculosis Beijing genotype strains comprise 50-80% in Russian Federation, which are divided into the main B0/W148, CladeA, and CAO clusters based on VNTR and SNP analysis. It should be noted that such phylogenetically highly close MTB strains belong to the modern Beijing family, generally demonstrating high transmissibility, association with drug resistance, and prevalence among patients with severe forms of the disease. However, studies on MTB genetic cluster strain-related virulence are scarce and contradictory. Here, we investigated virulence of diverse Mycobacterium tuberculosis strains belonging to the B0/W148, CladeA and CAO clusters and nonclustered strain NK of the Beijing family as well as laboratory strain H37Rv in C57BL/6 mice. It was found that mice infected with NK and B0/W148 vs. CladeA strains revealed the peak and the lowest mortality, respectively, while assessing survival rate in various groups (20 mice per MTB strain examined). Analyzing experimental data in mice demonstrated that all MTB strains were able to cause typical tuberculosis-related pathogenic signs. In particular, time-dependent evaluation of pathological changes (on 1, 3, 7, 14, 21, 28, 60 and 120 day post infection) in the lungs and spleen revealed significant differences among various strains. Tuberculosis progression was observed in the mice infected with B0/W148 and NK strains, whereas CladeA, CAO and H37Rv strains resulted in stabilized course and less marked organs damage. Moreover, we found that bacterial load after infection with Beijing family clustering strains was lower compared to that of the reference H37Rv strain, except NK strain demonstrating the peak bacterial load among the Beijing family comparable to H37Rv strain at 120 dpi. Thus, it was found that the level of virulence between most virulent B0/W148 cluster strain vs. NK strain was similar. Overall, the data obtained indicate that Beijing genotype strains are characterized by a diverse range of phenotypic virulence in vivo.

Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia

“…Similarly, in another Russian study, the bacterial load after infection with Beijing clustered strains was lower than that of H37Rv. B0/W148 cluster, known as transmissible, had a similar level of virulence as the non-clustered strain of the Central Asian/Russian clade [ 14 ]. However, in our study, we did demonstrate a correlation between the mortality rates of infected mice and the severity of pathological changes in the lung tissue, as well as the bacterial load in the lungs and spleen.…”

“…Keeping the issue of comparability in mind, we looked at our data in the light of the previous study of the modern Beijing sublineage in Russia [ 14 ]. Mouse studies are recognized to be extremely time-consuming and cannot target many strains.…”

“…Thus, an informed use of the previous results, whenever possible, is helpful. The above-cited study [ 14 ] was performed in the same laboratory of experimental tuberculosis under the same design and using the same strain H37Rv. The mice were obtained from the same animal nursery and both studies were carried out in the same period of the year (January-July 2018 and 2020).…”

“…Strain 6691 belongs to 1071-32- cluster (RD181 deleted), strain 396 belongs to 14717-15-cluster (RD181 intact). (b) modern Beijing sublineage (adapted from Bespyatykh et al [ 14 ]). B0/W148 strain is also named Russian epidemic or successful cluster.…”

“…Previously, the C57BL/6 resistant mice infected with highly virulent M. tuberculosis strain were shown as a TB model reproducing an exacerbated inflammatory response in a resistant host to hypervirulent mycobacteria, leading to irreversible necrotic lung lesions [ 13 ]. Properties of the Beijing strains were previously studied in this model, including ancient and modern sublineages from different countries [ 10 , 14 ]. However, only modern Beijing sublineage strains from Russia were analysed in those studies.…”