Clinically encountered growth phenotypes of tuberculosis-causing bacilli and their in vitro study: A review.

Clinically encountered growth phenotypes of tuberculosis-causing bacilli and their in vitro study: A review.
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临床遇到的结核杆菌生长表型及其体外研究:一篇综述。

DOI:
10.3389/fcimb.2022.1029111
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发表时间:
2022
影响因子:
5.7
通讯作者:
--
中科院分区:
医学2区
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--
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结核病 (TB) 的临床表现在严重程度、感染部位和治疗结果方面差异很大,因此需要同时努力安全地进行个体化治疗,并寻找可在整个临床范围内成功使用的更短的治疗方案。在这些努力中,临床医生和研究人员都采用富媒体中的分枝杆菌培养。然而,即使在同一患者体内,群体中的个体杆菌在其可培养性方面也可能表现出很大的变异性。体外芽孢杆菌在复制率和培养要求以及对抗菌药物杀死的敏感性方面也表现出显着的异质性。了解临床、离体和体外生长表型多样性的相似性可能是识别那些导致治疗失败、复发和使结核感染进展为疾病的杆菌重新激活的表型的关键。本综述简要总结了分枝杆菌培养目前在结核病患者护理中的作用以及结核病可培养性变异的离体证据。然后,我们讨论了体外模型的最新进展,这些模型研究遗传相同的大量培养物中的异质亚群,重点是氧化应激对细菌培养要求的影响。该综述强调了分枝杆菌生长的异质性给临床环境和研究中的培养解释带来的复杂性。它还强调了生长表型和抗菌敏感性之间相互作用的复杂性。更好地了解人口动态和随时间和空间的增长需求有望有助于个体化结核病治疗和寻找统一有效的治疗方法。
The clinical manifestations of tuberculosis (TB) vary widely in severity, site of infection, and outcomes of treatment—leading to simultaneous efforts to individualize therapy safely and to search for shorter regimens that can be successfully used across the clinical spectrum. In these endeavors, clinicians and researchers alike employ mycobacterial culture in rich media. However, even within the same patient, individual bacilli among the population can exhibit substantial variability in their culturability. Bacilli in vitro also demonstrate substantial heterogeneity in replication rate and cultivation requirements, as well as susceptibility to killing by antimicrobials. Understanding parallels in clinical, ex vivo and in vitro growth phenotype diversity may be key to identifying those phenotypes responsible for treatment failure, relapse, and the reactivation of bacilli that progresses TB infection to disease. This review briefly summarizes the current role of mycobacterial culture in the care of patients with TB and the ex vivo evidence of variability in TB culturability. We then discuss current advances in in vitro models that study heterogenous subpopulations within a genetically identical bulk culture, with an emphasis on the effect of oxidative stress on bacillary cultivation requirements. The review highlights the complexity that heterogeneity in mycobacterial growth brings to the interpretation of culture in clinical settings and research. It also underscores the intricacies present in the interplay between growth phenotypes and antimicrobial susceptibility. Better understanding of population dynamics and growth requirements over time and space promises to aid both the attempts to individualize TB treatment and to find uniformly effective therapies.
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