title: Label-free, rapid and quantitative phenotyping of stress response in E. coli via ramanome.
abstract: Rapid profiling of stress-response at single-cell resolution yet in a label-free, non-disruptive and mechanism-specific manner can lead to many new applications. We propose a single-cell-level biochemical fingerprinting approach named "ramanome", which is the collection of Single-cell Raman Spectra (SCRS) from a number of cells randomly selected from an isogenic population at a given time and condition, to rapidly and quantitatively detect and characterize stress responses of cellular population. SCRS of Escherichia coli cells are sensitive to both exposure time (eight time points) and dosage (six doses) of ethanol, with detection time as early as 5 min and discrimination rate of either factor over 80%. Moreover, the ramanomes upon six chemical compounds from three categories, including antibiotics of ampicillin and kanamycin, alcohols of ethanol and n-butanol and heavy metals of Cu2+and Cr6+, were analyzed and 31 marker Raman bands were revealed which distinguish stress-responses via cytotoxicity mechanism and variation of inter-cellular heterogeneity. Furthermore, specificity, reproducibility and mechanistic basis of ramanome were validated by tracking stress-induced dynamics of metabolites and by contrasting between cells with and without genes that convey stress resistance. Thus ramanome enables rapid prediction and mechanism-based screening of cytotoxicity and stress-response programs at single-cell resolution.
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Teng
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Honglei
authors.initials: H
authors.lastname: Gou
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Ren
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Yuetong
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Engineering, University of Oxford, Oxford, Parks Road, OX1 3PJ, UK.
authors.forename: Wei E
authors.initials: WE
authors.lastname: Huang
authors.affiliation: Single-Cell Center, CAS Key Laboratory of Biofuels and Shandong Key Laboratory of Energy Genetics, Qingdao Institute of BioEnergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
mesh_terms: D000438:Alcohols / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism*; D019216:Metals, Heavy / Q000494:pharmacology*; D013059:Spectrum Analysis, Raman / Q000379:methods*; D013312:Stress, Physiological / Q000187:drug effects*
chemical_list: D000438:Alcohols; D000900:Anti-Bacterial Agents; D019216:Metals, Heavy