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Small Molecule Sensors Targeting the Bacterial Cell Wall.
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2020-05-20 , DOI: 10.1021/acsinfecdis.9b00515
Matthew F L Parker 1 , Robert R Flavell 1 , Justin M Luu 1 , Oren S Rosenberg 2 , Michael A Ohliger 1, 3 , David M Wilson 1
Affiliation  

This review highlights recent efforts to detect bacteria using engineered small molecules that are processed and incorporated similarly to their natural counterparts. There are both scientific and clinical justifications for these endeavors. The use of detectable, cell-wall targeted chemical probes has elucidated microbial behavior, with several fluorescent labeling methods in widespread laboratory use. Furthermore, many existing efforts including ours, focus on developing new imaging tools to study infection in clinical practice. The bacterial cell wall, a remarkably rich and complex structure, is an outstanding target for bacteria-specific detection. Several cell wall components are found in bacteria but not mammals, especially peptidoglycan, lipopolysaccharide, and teichoic acids. As this review highlights, the development of laboratory tools for fluorescence microscopy has vastly outstripped related positron emission tomography (PET) or single photon emission computed tomography (SPECT) radiotracer development. However, there is great synergy between these chemical strategies, which both employ mimicry of endogenous substrates to incorporate detectable structures. As the field of bacteria-specific imaging grows, it will be important to understand the mechanisms involved in microbial incorporation of radionuclides. Additionally, we will highlight the clinical challenges motivating this imaging effort.

中文翻译:

靶向细菌细胞壁的小分子传感器。

这篇综述着重介绍了最近使用工程化小分子检测细菌的努力,这些小分子的加工和掺入方法与其天然对应物相似。这些努力既有科学依据,也有临床依据。可检测的细胞壁靶向化学探针的使用阐明了微生物的行为,在广泛的实验室应用中采用了几种荧光标记方法。此外,包括我们在内的许多现有努力都致力于开发新的成像工具来研究临床实践中的感染。细菌细胞壁非常丰富且复杂,是细菌特异性检测的出色靶标。在细菌中发现了几种细胞壁成分,在哺乳动物中却没有,尤其是肽聚糖,脂多糖和磷壁酸。正如这篇评论所强调的那样,荧光显微镜实验室工具的开发已经远远超过了相关的正电子发射断层扫描(PET)或单光子发射计算机断层扫描(SPECT)放射性示踪剂的开发。但是,这些化学策略之间都具有巨大的协同作用,它们都采用模仿内源性底物的方式来结合可检测的结构。随着细菌特异性成像领域的发展,了解参与放射性核素微生物掺入的机制将非常重要。此外,我们将重点介绍激发这种成像努力的临床挑战。两者均采用内源性底物的拟态结合可检测的结构。随着细菌特异性成像领域的发展,了解参与放射性核素微生物掺入的机制将非常重要。此外,我们将重点介绍激发这种成像努力的临床挑战。两者均采用内源性底物的拟态结合可检测的结构。随着细菌特异性成像领域的发展,了解参与放射性核素微生物掺入的机制将非常重要。此外,我们将重点介绍激发这种成像努力的临床挑战。
更新日期:2020-07-10
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