Chemical fingerprint of bacteriophages by infrared nano-spectroscopy

Bacteriophage (phages) are naturally occurring nanoscale antimicrobial agents that can self-replicate at infection sites and selectively eliminate pathogenic bacteria. Significant heterogeneity exists in phage properties such as morphology, protein and nucleic acid composition, subject to the strain, state, and environment of the phage source. However, current techniques fall short in accurately mapping the chemical compositions of individual phages. A thorough understanding of this heterogeneity is essential to elucidate the difference between phage types and their stability, which may impact phages as effective therapeutic agents. We propose using scattering scanning near-field optical microscopy (s-SNOM) as an innovative method to map the chemical composition of phages at the nanoscale. The strength of this method lies in its label-free, ultra-high sensitivity that measures individual phage chemical heterogeneity. Additionally, s-SNOM is ideal for thermally sensitive phages, as it detects light scattered by nanoscale specimens without relying on thermal expansion. New insights from this method into phage chemical composition will profoundly impact our understanding of phage biology and optimise phage formulation for therapeutic use.