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Metabolic-Activity-Based Assessment of Antimicrobial Effects by D2O-Labeled Single-Cell Raman Microspectroscopy
Tao, Yifan1,2,3; Wang, Yun2,3; Huang, Shi2,3; Zhu, Pengfei2,3; Huang, Wei E.4; Ling, Junqi1; Xu, Jian2,3,5
2017-04-04
发表期刊ANALYTICAL CHEMISTRY
卷号89期号:7页码:4108-4115
摘要To combat the spread of antibiotic resistance, methods that quantitatively assess the metabolism-inhibiting effects of drugs in a rapid and culture-independent manner are urgently needed. Here using four oral bacteria as models, we show that heavy water (D2O)-based single-cell Raman micro- spectroscopy (D2O-Raman) can probe bacterial response to different drugs using the Raman shift at the C-D (carbon deuterium vibration) band in 2040 to 2300 cm(-1) as a universal biomarker for metabolic activity at single-bacterial-cell resolution. The "minimum inhibitory concentration based on metabolic activity" (MIC-MA), defined as the minimal dose under which the median Delta CD-ratio at 8 h of drug exposure is <= 0 and the standard deviation (SD) of the Delta C-D ratio among, individual cells is <= 0.005, was proposed to evaluate the metabolism-inhibiting efficacy of drugs. In addition, heterogeneity index of MIC-MA (MIC-MA-HI), defined as SD of C-D ratio, among individual cells, quantitatively assesses the among-cell heterogeneity of metabolic activity after drug regimens. When exposed to 1 X MIC of sodium fluoride (NaF), 1 X MIC of chlorhexidine (CHX), or 60 X MIC of ampicillin, the cariogenic oral pathogen Streptococcus mutans UA159 ceased propagation yet remained metabolically highly active. This underscores the advantage of MIC-MA over the growth-based MIC in being able to detect the "nongrowing but metabolically active" (NGMA) cells that underlie many latent or recurring infections. Moreover, antibiotic susceptible and resistant S. mutans strains can be readily discriminated at as early as 0.5 h. Thus, D2O-Raman can serve as a universal method for rapid and quantitative assessment of antimicrobial effects based on general metabolic activity at single-cell resolution.
文章类型Article
WOS标题词Science & Technology ; Physical Sciences
DOI10.1021/acs.analchem.6b05051
关键词[WOS]MYCOBACTERIUM-TUBERCULOSIS ; PHENOTYPIC HETEROGENEITY ; STREPTOCOCCUS-MUTANS ; ESCHERICHIA-COLI ; IN-VITRO ; RESISTANCE ; STRESS ; BIOLUMINESCENCE ; SPECTROSCOPY ; INHIBITION
收录类别SCI
语种英语
WOS研究方向Chemistry
项目资助者NSFC(91231205 ; CAS(XDB15040100 ; Shandong Province(2015ZDJS04002) ; EPSRC(EP/M002403/1) ; NERC in the UK(NE/M002934/1) ; China Postdoctoral Science Foundation(2016LH00036) ; 81430011 ; KFJSW-STS-165 ; 31327001 ; QYZDB-SSW-SMC015) ; 31425002 ; 31400436 ; 31400089)
WOS类目Chemistry, Analytical
WOS记录号WOS:000398645300043
引用统计
文献类型期刊论文
条目标识符http://ir.qibebt.ac.cn/handle/337004/9298
专题单细胞中心组群
作者单位1.Sun Yat Sen Univ, Guangdong Prov Key Lab Stomatol, Affiliated Stomatol Hosp, Operat Dent & Endodont,Guanghua Sch Stomatol, Guangzhou 510055, Guangdong, Peoples R China
2.Chinese Acad Sci, Qingdao Inst BioEnergy & Bioproc Technol, CAS Key Lab Biofuels, Single Cell Ctr, Qingdao 266101, Shandong, Peoples R China
3.Chinese Acad Sci, Qingdao Inst BioEnergy & Bioproc Technol, Shandong Key Lab Energy Genet, Qingdao 266101, Shandong, Peoples R China
4.Univ Oxford, Dept Engn Sci, Parks Rd, Oxford OX1 3PJ, England
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
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GB/T 7714
Tao, Yifan,Wang, Yun,Huang, Shi,et al. Metabolic-Activity-Based Assessment of Antimicrobial Effects by D2O-Labeled Single-Cell Raman Microspectroscopy[J]. ANALYTICAL CHEMISTRY,2017,89(7):4108-4115.
APA Tao, Yifan.,Wang, Yun.,Huang, Shi.,Zhu, Pengfei.,Huang, Wei E..,...&Xu, Jian.(2017).Metabolic-Activity-Based Assessment of Antimicrobial Effects by D2O-Labeled Single-Cell Raman Microspectroscopy.ANALYTICAL CHEMISTRY,89(7),4108-4115.
MLA Tao, Yifan,et al."Metabolic-Activity-Based Assessment of Antimicrobial Effects by D2O-Labeled Single-Cell Raman Microspectroscopy".ANALYTICAL CHEMISTRY 89.7(2017):4108-4115.
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