Raman spectra identify heterogeneous vancomycin resistance and transcriptomes ofStaphylococcus aureus

Abstract

Staphylococcus aureusis a pathogenic bacterium that has caused multiple epidemics linked with the emergence of new antibiotic resistance. Vancomycin is the first-line antibiotic to treat methicillin-resistantS. aureus(MRSA) infection. However, several types of vancomycin nonsusceptible MRSA strains have been recognized to date. Although rapid assessment of their resistance levels and underlying molecular profiles are crucial for preventing their spread and counteracting resistance, the broad resistance spectrum and the diversity of genetic changes have impeded the practice. Here, we show that Raman spectra obtained from single cells can elucidate vancomycin resistance levels and global transcriptomic profiles of different MRSA strains. Dimension reduction and classification of Raman spectra reveal common cellular state changes linked with vancomycin susceptibility and differences among the strains with equivalent resistance. Furthermore, Raman spectra predicted more significant phenotypic heterogeneity in a population of a vancomycin-intermediate strain, which was confirmed by single-cell growth analysis. Therefore, these results demonstrate that antibiotic resistance, gene expression profiles, and phenotypic heterogeneity can be interrogated spectroscopically without laborious assays and sample preparation. Overall, our findings underscore the potential of Raman spectroscopy as a powerful and versatile tool in the ongoing battle against antibiotic resistance.