Surface-Enhanced Raman Spectroscopy of Bacterial Metabolites for Bacterial Growth Monitoring and Diagnosis of Viral Infection.

Bacterial metabolites are intermediate products of bacterial metabolism and their production reflects metabolic activity. Herein, we report the use of surface-enhanced Raman spectroscopy (SERS) for detection of both volatile and nonvolatile metabolites and the application of this approach for bacterial growth quantification and diagnosis of viral infection. The time-dependent SERS signal of the volatile metabolite dimethyl disulfide in the headspace above bacteria growing on an agar plate was detected and quantified. In addition, SERS signals arising from the plate reflected nutrient consumption and production of nonvolatile metabolites. The measurement of metabolite accumulation can be used for bacterial quantification. In the presence of bacteriophage virus, bacterial metabolism is suppressed, and the relative decrease in SERS intensity reflects the initial virus concentration. Using multivariate analysis, we detect viral infection with a prediction accuracy of 93%. Our SERS-based approach for metabolite production monitoring provides new insights toward viral infection diagnosis.