Choi Honggu, Li Zhe, Hua Zhen, Zuponcic Jessica, Ximenes Eduardo, Turek John J, Ladisch Michael R, Nolte David D
Department of Physics and Astronomy, Purdue University, 525 Northwestern Ave, West Lafayette, IN, 47907, USA.
Department of Agricultural and Biological Engineering and the Laboratory of Renewable Resources Engineering, Purdue University, West Lafayette, IN, 47907, USA.
Commun Biol. 2021 Feb 10;4(1):178. doi: 10.1038/s42003-020-01550-8.
Living 3D in vitro tissue cultures, grown from immortalized cell lines, act as living sentinels as pathogenic bacteria invade the tissue. The infection is reported through changes in the intracellular dynamics of the sentinel cells caused by the disruption of normal cellular function by the infecting bacteria. Here, the Doppler imaging of infected sentinels shows the dynamic characteristics of infections. Invasive Salmonella enterica serovar Enteritidis and Listeria monocytogenes penetrate through multicellular tumor spheroids, while non-invasive strains of Escherichia coli and Listeria innocua remain isolated outside the cells, generating different Doppler signatures. Phase distributions caused by intracellular transport display Lévy statistics, introducing a Lévy-alpha spectroscopy of bacterial invasion. Antibiotic treatment of infected spheroids, monitored through time-dependent Doppler shifts, can distinguish drug-resistant relative to non-resistant strains. This use of intracellular Doppler spectroscopy of living tissue sentinels opens a new class of microbial assay with potential importance for studying the emergence of antibiotic resistance.
由永生化细胞系培养而成的活的三维体外组织培养物，在致病细菌侵入组织时充当活的哨兵。感染通过感染细菌破坏正常细胞功能导致哨兵细胞内动力学变化来报告。在此，受感染哨兵的多普勒成像显示了感染的动态特征。侵袭性肠炎沙门氏菌血清型肠炎菌株和单核细胞增生李斯特菌穿透多细胞肿瘤球体，而非侵袭性大肠杆菌菌株和无害李斯特菌则停留在细胞外，产生不同的多普勒信号。由细胞内运输引起的相位分布呈现 Lévy 统计，引入了细菌入侵的 Lévy-α 光谱学。通过随时间变化的多普勒频移监测对感染球体进行抗生素治疗，可以区分耐药菌株和非耐药菌株。这种对活组织哨兵进行细胞内多普勒光谱分析的方法开辟了一类新的微生物检测方法，对研究抗生素耐药性的出现具有潜在重要意义。
