Dynamic insights into increasing antibiotic resistance in Staphylococcus aureus by label-free SERS using a portable Raman spectrometer

Rapid and quantitative detection of bacterial antibiotic resistance is of great significance for the prevention and treatment of infections and understanding drug-resistant mechanism. In this study, label-free surface-enhanced Raman spectroscopy (SERS) technology was applied to dynamically explore oxacillin/cefazolin-derived resistance in Staphylococcus aureus using a portable Raman spectrometer. The results showed that S. aureus rapidly responded to oxacillin/cefazolin stimulation and gradually developed different degrees of drug resistance during the 21 days of exposure. The molecular changes that accumulated in the drug-resistant strains were sensitively recorded by SERS in a whole-cell manner. Principal components-linear discriminant analysis correctly distinguished various degrees of drug-resistant strains. The typical Raman peak intensities of I734/I867 showed a negative and non-linear correlation with the minimum inhibitory concentration (MIC). The correlation coefficient reached above 0.9. The target sites of oxacillin/cefazolin on S. aureus clearly reflected on SERS profiles. The results collected by SERS were further verified by other biological methods including the antibiotic susceptibility test, MIC determination, and PCR results. This study indicates that SERS technology provides a rapid and flexible alternative to current drug susceptibility testing, laying a foundation for qualitative and quantitative evaluation of drug resistance in clinical detection.