GLOBAL PHOSPHOPROTEOMIC ANALYSIS OF MYCOBACTERIOPHAGE – MYCOBACTERIA INTERACTION

Mycobacteriophages are viruses that prey on bacteria and exploit the host's biological resources to proliferate. They have evolved extensively and are among the most common and genetically varied species on Earth. The increasing incidence of antimicrobial resistance (AMR) and the slow discovery of novel antibacterials have recently sparked a renewed interest in phage therapy.

Cells can interact with one another and with their external environment as well as with other components of the cell via signal transduction pathways, which are frequently connected to changes in protein phosphorylation. The two-component system (TCS), made up of the cytosolic transcriptional response regulator (RR) and the membrane-bound sensor histidine kinase (HK) is essential for mycobacteria to identify and react to external cues. It has been demonstrated that mycobacteria's post translational modifications (PTMs) control and promote essential biological functions, including as central metabolism, and pathogenicity, but their role is not always well understood. Current mycobacteria phosphoproteomic applications have been focused on qualitative data without quantitative research. This research utilized the YemiJoy2021 lytic cluster C1 phage to infect Mycobacterium smegmatis during its mid-stationary growth phase. The study is groundbreaking in its approach, as it introduces a novel mass spectrometry (MS) protocol specifically designed for analyzing phage phosphoproteomics over time. The identification of specific phosphosites and temporal changes in phosphorylation patterns will provide valuable insights to biological mechanisms behind the anti-mycobacterial activities of mycobacteriophages. The findings of this study may influence the creation of innovative preventative techniques for mycobacterial infections and advancing precision medicine approaches in infectious disease management.