Evolution of Drug-Resistant Mycobacterium tuberculosis Strains and Their Adaptation to the Human Lung Environment.
Evolution of Drug-Resistant Mycobacterium tuberculosis Strains and Their Adaptation to the Human Lung Environment.
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DOI：
10.3389/fmicb.2021.612675
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发表时间：
2021
影响因子：
5.2
通讯作者：
Torrelles JB
中科院分区：
文献类型：
--
作者：
Allué-Guardia A;García JI;Torrelles JB
在过去的二十年里，多重(MDR)、广谱(XDR)、极端(XXDR)和完全(TDR)耐药结核分枝杆菌(M.tb)菌株已成为对全球公共卫生的威胁，强调了制定新的结核病预防和治疗策略的必要性。据估计，在接下来的35年里，耐药结核病将导致约7500万人死亡，给全球经济造成16.7万亿美元的损失。事实上，由于缺乏资源和在结核病流行地区强制隔离，仅新冠肺炎一次大流行就可能导致630万新结核病病例的发展。耐药结核分枝杆菌的进化取决于许多因素，如细菌适合度、菌株的遗传背景和适应周围环境的能力，以及宿主特有的和环境因素。近年来，全基因组转录组学和全基因组关联研究为结核分枝杆菌耐药性的复杂性提供了一些见解，并提供了对其潜在分子机制的更好理解。在这篇综述中，我们将讨论驱动耐药的结核分枝杆菌的表型和基因变化，包括细胞膜成分的变化，以及最近描述的促进耐药产生和传播的内在和外在因素。我们将进一步探索耐药结核分枝杆菌如何在细胞水平上与敏感菌株在肺环境中不同地适应，调节结核分枝杆菌与宿主的相互作用和疾病结果，以及研究耐药结核的新的下一代测序(NGS)策略。
In the last two decades, multi (MDR), extensively (XDR), extremely (XXDR) and total (TDR) drug-resistant Mycobacterium tuberculosis (M.tb) strains have emerged as a threat to public health worldwide, stressing the need to develop new tuberculosis (TB) prevention and treatment strategies. It is estimated that in the next 35 years, drug-resistant TB will kill around 75 million people and cost the global economy $16.7 trillion. Indeed, the COVID-19 pandemic alone may contribute with the development of 6.3 million new TB cases due to lack of resources and enforced confinement in TB endemic areas. Evolution of drug-resistant M.tb depends on numerous factors, such as bacterial fitness, strain’s genetic background and its capacity to adapt to the surrounding environment, as well as host-specific and environmental factors. Whole-genome transcriptomics and genome-wide association studies in recent years have shed some insights into the complexity of M.tb drug resistance and have provided a better understanding of its underlying molecular mechanisms. In this review, we will discuss M.tb phenotypic and genotypic changes driving resistance, including changes in cell envelope components, as well as recently described intrinsic and extrinsic factors promoting resistance emergence and transmission. We will further explore how drug-resistant M.tb adapts differently than drug-susceptible strains to the lung environment at the cellular level, modulating M.tb–host interactions and disease outcome, and novel next generation sequencing (NGS) strategies to study drug-resistant TB.
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