Impact of pathobiological diversity of Mycobacterium tuberculosis on clinical features and lethal outcome of tuberculosis

Igor Mokrousov,Oksana Pasechnik,Anna Vyazovaya,Viacheslav Zhuravlev,Aleksey Blokh,Irina Yarusova,Alena Gerasimova

doi:10.1186/s12866-022-02461-w

Abstract

BackgroundMycobacterium tuberculosis population in Russia is dominated by the notorious Beijing genotype whose major variants are characterized by contrasting resistance and virulence properties. Here we studied how these strain features could impact the progression of pulmonary tuberculosis (TB) concerning clinical manifestation and lethal outcome.ResultsThe study sample included 548 M. tuberculosis isolates from 548 patients with newly diagnosed pulmonary TB in Omsk, West Siberia, Russia. Strains were subjected to drug susceptibility testing and genotyping to detect lineages, sublineages, and subtypes (within Beijing genotype). The Beijing genotype was detected in 370 (67.5%) of the studied strains. The strongest association with multidrug resistance (MDR) was found for epidemic cluster Beijing B0/W148 (modern sublineage) and two recently discovered MDR clusters 1071–32 and 14717–15 of the ancient Beijing sublineage. The group of patients infected with hypervirulent and highly lethal (in a mouse model) Beijing 14717–15 showed the highest rate of lethal outcome (58.3%) compared to Beijing B0/W148 (31.4%; P = 0.06), Beijing Central Asian/Russian (29.7%, P = 0.037), and non-Beijing (15.2%, P = 0.001). The 14717–15 cluster mostly included isolates from patients with infiltrative but not with fibrous-cavernous and disseminated TB. In contrast, a group infected with low virulent 1071–32-cluster had the highest rate of fibrous-cavernous TB, possibly reflecting the capacity of these strains for prolonged survival and chronicity of the TB process.ConclusionsThe group of patients infected with hypervirulent and highly lethal in murine model 14717–15 cluster had the highest proportion of the lethal outcome (58.3%) compared to the groups infected with Beijing B0/W148 (31.4%) and non-Beijing (15.2%) isolates. This study carried out in the TB high-burden area highlights that not only drug resistance but also strain virulence should be considered in the implementation of personalized TB treatment.

Highlights

Recognition of the clinical significance of Mycobacterium tuberculosis population diversity is the key issue in molecular epidemiology and personalized medicine of tuberculosis (TB)
M. tuberculosis population in Russia is dominated by the Beijing genotype which major epidemic and endemic variants are characterized by contrasting drug resistance and virulence
The Beijing genotype as a whole was associated with an multidrug resistance (MDR) phenotype but members of some Beijing subtypes were significantly more likely to be MDR

Summary

Introduction

Recognition of the clinical significance of Mycobacterium tuberculosis population diversity is the key issue in molecular epidemiology and personalized medicine of tuberculosis (TB). In Russia, such important Beijing clusters are represented by two major and endemic genotypes B0/W148 ( termed as Russian epidemic/successful strain [11]) and Central Asian/Russian [12]. Both are widespread across all Russia and other countries of the Former Soviet Union but differ in association with drug resistance, B0/W148 being the most dangerous. Mycobacterium tuberculosis population in Russia is dominated by the notorious Beijing genotype whose major variants are characterized by contrasting resistance and virulence properties. We studied how these strain features could impact the progression of pulmonary tuberculosis (TB) concerning clinical manifestation and lethal outcome

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Conclusion