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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
Source PublicationANALYTICAL CHEMISTRY
Volume89Issue:7Pages:4108-4115
AbstractTo 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.
SubtypeArticle
WOS HeadingsScience & Technology ; Physical Sciences
DOI10.1021/acs.analchem.6b05051
WOS KeywordMYCOBACTERIUM-TUBERCULOSIS ; PHENOTYPIC HETEROGENEITY ; STREPTOCOCCUS-MUTANS ; ESCHERICHIA-COLI ; IN-VITRO ; RESISTANCE ; STRESS ; BIOLUMINESCENCE ; SPECTROSCOPY ; INHIBITION
Indexed BySCI
Language英语
WOS Research AreaChemistry
Funding OrganizationNSFC(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 SubjectChemistry, Analytical
WOS IDWOS:000398645300043
Citation statistics
Document Type期刊论文
Identifierhttp://ir.qibebt.ac.cn/handle/337004/9298
Collection单细胞中心组群
Affiliation1.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
Recommended Citation
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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