Building Spatiotemporal Understanding of Mycobacterium tuberculosis-Host Interactions.

IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL
ACS Infectious Diseases Pub Date : 2025-02-14 Epub Date: 2025-01-23 DOI:10.1021/acsinfecdis.4c00840
Anna-Lisa E Lawrence, Shumin Tan
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引用次数: 0

Abstract

Heterogeneity during Mycobacterium tuberculosis (Mtb) infection greatly impacts disease outcome and complicates treatment. This heterogeneity encompasses many facets, spanning local differences in the host immune response to Mtb and the environment experienced by the bacterium, to nonuniformity in Mtb replication state. All of these facets are interlinked and each can affect Mtb susceptibility to antibiotic treatment. In-depth spatiotemporal understanding of Mtb-host interactions is thus critical to both fundamental comprehension of Mtb infection biology and for the development of effective therapeutic regimens. Such spatiotemporal understanding dictates the need for analysis at the single bacterium/cell level in the context of intact tissue architecture, which has been a significant technical challenge. Excitingly, innovations in spatial single cell methodology have opened the door to such studies, beginning to illuminate aspects ranging from intergranuloma differences in cellular composition and phenotype, to sublocation differences in Mtb physiology and replication state. In this perspective, we discuss recent studies that demonstrate the potential of these methodological advancements to reveal critical spatiotemporal insight into Mtb-host interactions, and highlight future avenues of research made possible by these advances.

构建结核分枝杆菌-宿主相互作用的时空理解。
结核分枝杆菌(Mtb)感染期间的异质性极大地影响了疾病结局并使治疗复杂化。这种异质性包括许多方面,从宿主对结核分枝杆菌的免疫反应和细菌所经历的环境的局部差异,到结核分枝杆菌复制状态的不均匀性。所有这些方面都是相互关联的,每个方面都可能影响结核分枝杆菌对抗生素治疗的易感性。因此,深入了解结核分枝杆菌与宿主相互作用的时空关系对于理解结核分枝杆菌感染生物学的基础知识和制定有效的治疗方案至关重要。这样的时空理解决定了在完整组织结构的背景下,需要在单个细菌/细胞水平上进行分析,这是一个重大的技术挑战。令人兴奋的是,空间单细胞方法的创新为这类研究打开了大门,开始阐明从细胞组成和表型的肉芽肿间差异到结核分枝杆菌生理和复制状态的亚位差异等方面。从这个角度来看,我们讨论了最近的研究,这些研究证明了这些方法进步的潜力,揭示了线粒体-宿主相互作用的关键时空洞察力,并强调了这些进步使未来的研究途径成为可能。
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来源期刊
ACS Infectious Diseases
ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES
CiteScore
9.70
自引率
3.80%
发文量
213
期刊介绍: ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.
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