REVIEW: Interaction of Mycobacterium tuberculosis with the Host from the Pathogen’s Perspective

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Vladimir V. Yeremeev¹ and Galina S. Shepelkova^1,a*

¹Central Tuberculosis Research Institute, 107564 Moscow, Russia

^* To whom correspondence should be addressed.

Received: September 23, 2025; Revised: October 21, 2025; Accepted: October 24, 2025

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Since the Mycobacterium tuberculosis genome was decoded in 1998, our understanding of this dangerous pathogen – which has become the leading cause of bacterial infection-related deaths in modern human history – has expanded significantly. This review examines genetic, physiological, and metabolic factors believed to play a key role in the adaptation strategies of M. tuberculosis to survival within the human host. These strategies underpin critical aspects of the bacterium life cycle, including infection, persistence, dissemination, and transmission to the new hosts. We also discuss how M. tuberculosis adapts to the primary factors of the host’s innate and adaptive immunity, including their roles in disease progression. Granulocyte migration, phagosome damage and repair, autophagy, and cell death are pivotal processes that determine outcome of the host–mycobacterium interactions. To date, experimental evidence has accumulated indicating that small bacterial RNAs play a crucial role in regulating numerous physiological processes and key stages of the pathogen life cycles. Our review explores the hypothesis that M. tuberculosis small RNAs may not only adapt the bacterial transcriptome to changing conditions but also interact with the transcriptome of the infected host, interfering with antibacterial defense processes. Given the growing recognition of the significance of asymptomatic infection and transmission of M. tuberculosis, we argue for stronger integration between the laboratory and clinical research in this field.

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KEY WORDS: M. tuberculosis, tuberculosis, host immune evasion, adaptation, non-coding RNAs

DOI: 10.1134/S0006297925603302

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