Salina Elena G, Makarov Vadim
Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, Russia.
Microorganisms. 2022 Nov 25;10(12):2334. doi: 10.3390/microorganisms10122334.
Both latent and active TB infections are caused by a heterogeneous population of mycobacteria, which includes actively replicating and dormant bacilli in different proportions. Dormancy substantially affects drug tolerance and TB clinical management due to a significant decrease in the metabolic activity of bacilli, which leads to the complexity of both the diagnosis and the eradication of bacilli. Most diagnostic approaches to latent infection deal with a subpopulation of active , underestimating the contribution of dormant bacilli and leading to limited success in the fight against latent TB. Moreover, active TB appears not only as a primary form of infection but can also develop from latent TB, when resuscitation from dormancy is followed by bacterial multiplication, leading to disease progression. To win against latent infection, the identification of the Achilles' heel of dormant is urgently needed. Regulatory mechanisms and metabolic adaptation to growth arrest should be studied using and models that adequately imitate latent TB infection in macroorganisms. Understanding the mechanisms underlying dormancy and resuscitation may provide clues to help control latent infection, reduce disease severity in patients, and prevent pathogen transmission in the population.
潜伏性和活动性结核感染均由多种结核分枝杆菌引起，这些结核分枝杆菌包括不同比例的活跃复制菌和休眠菌。由于杆菌代谢活性显著降低，休眠状态极大地影响了药物耐受性和结核病的临床管理，这导致了杆菌诊断和根除的复杂性。大多数针对潜伏感染的诊断方法针对的是活跃菌亚群，低估了休眠菌的作用，导致在对抗潜伏性结核病方面成效有限。此外，活动性结核病不仅表现为原发性感染形式，也可由潜伏性结核病发展而来，即从休眠状态复苏后细菌繁殖，导致疾病进展。为战胜潜伏感染，迫切需要找出休眠菌的致命弱点。应使用能充分模拟大型生物体中潜伏性结核感染的模型，研究调节机制和对生长停滞的代谢适应。了解休眠和复苏的潜在机制可能为控制潜伏感染、降低患者疾病严重程度以及防止病原体在人群中传播提供线索。
