An Isotope-Labeled Single-Cell Raman Spectroscopy Approach for Tracking the Physiological Evolution Trajectory of Bacteria toward Antibiotic Resistance |
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Authors: | Dr Kai Yang Fei Xu Longji Zhu Dr Hongzhe Li Prof Qian Sun Prof Aixin Yan Prof Bin Ren Prof Yong-Guan Zhu Prof Li Cui |
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Institution: | 1. Key Lab of Urban Environment and Health, Fujian Key Laboratory of Watershed Ecology, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, 361021 China;2. School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, China;3. State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 China |
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Abstract: | Understanding evolution of antibiotic resistance is vital for containing its global spread. Yet our ability to in situ track highly heterogeneous and dynamic evolution is very limited. Here, we present a new single-cell approach integrating D2O-labeled Raman spectroscopy, advanced multivariate analysis, and genotypic profiling to in situ track physiological evolution trajectory toward resistance. Physiological diversification of individual cells from isogenic population with cyclic ampicillin treatment is captured. Advanced multivariate analysis of spectral changes classifies all individual cells into four subsets of sensitive, intrinsic tolerant, evolved tolerant and resistant. Remarkably, their dynamic shifts with evolution are depicted and spectral markers of each state are identified. Genotypic analysis validates the phenotypic shift and provides insights into the underlying genetic basis. The new platform advances rapid phenotyping resistance evolution and guides evolution control. |
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Keywords: | Antibiotic Resistance Antibiotic Tolerance Evolution Trajectory Physiological Response Single Cell Raman Spectroscopy |
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