Grzeszczuk Zuzanna, Rosillo Antoinette, Owens Óisín, Bhattacharjee Sourav
School of Physics, Technological University Dublin, Dublin, Ireland.
School of Veterinary Medicine, University College Dublin (UCD), Dublin, Ireland.
Front Pharmacol. 2020 Oct 2;11:517165. doi: 10.3389/fphar.2020.517165. eCollection 2020.
The worldwide emergence of antimicrobial resistance (AMR) in pathogenic microorganisms, including bacteria and viruses due to a plethora of reasons, such as genetic mutation and indiscriminate use of antimicrobials, is a major challenge faced by the healthcare sector today. One of the issues at hand is to effectively screen and isolate resistant strains from sensitive ones. Utilizing the distinct nanomechanical properties (e.g., elasticity, intracellular turgor pressure, and Young's modulus) of microbes can be an intriguing way to achieve this; while atomic force microscopy (AFM), with or without modification of the tips, presents an effective way to investigate such biophysical properties of microbial surfaces or an entire microbial cell. Additionally, advanced AFM instruments, apart from being compatible with aqueous environments-as often is the case for biological samples-can measure the adhesive forces acting between AFM tips/cantilevers (conjugated to bacterium/virion, substrates, and molecules) and target cells/surfaces to develop informative force-distance curves. Moreover, such force spectroscopies provide an idea of the nature of intercellular interactions (e.g., receptor-ligand) or propensity of microbes to aggregate into densely packed layers, that is, the formation of -a property of resistant strains (e.g., ). This mini-review will revisit the use of single-cell force spectroscopy (SCFS) and single-molecule force spectroscopy (SMFS) that are emerging as powerful additions to the arsenal of researchers in the struggle against resistant microbes, identify their strengths and weakness and, finally, prioritize some future directions for research.
由于多种原因,包括基因突变和抗菌药物的滥用,致病微生物(包括细菌和病毒)中抗菌药物耐药性(AMR)在全球范围内出现,这是当今医疗保健部门面临的一项重大挑战。当前面临的问题之一是有效地从敏感菌株中筛选和分离出耐药菌株。利用微生物独特的纳米力学特性(例如弹性、细胞内膨压和杨氏模量)可能是实现这一目标的一种有趣方法;而原子力显微镜(AFM),无论探针是否经过修饰,都是研究微生物表面或整个微生物细胞这种生物物理特性的有效方法。此外,先进的AFM仪器,除了与水性环境兼容(生物样品通常如此)外,还可以测量作用于AFM探针/悬臂(与细菌/病毒粒子、底物和分子结合)与靶细胞/表面之间的粘附力,以绘制出信息丰富的力-距离曲线。而且,这种力谱学能提供关于细胞间相互作用(例如受体-配体)性质的概念,或者微生物聚集成致密堆积层的倾向,即形成耐药菌株的一种特性(例如 )。本综述将重新审视单细胞力谱学(SCFS)和单分子力谱学(SMFS)的应用,它们正成为对抗耐药微生物的研究人员武器库中强大的补充手段,识别它们的优缺点,最后确定一些未来的研究方向。