Exploring the Antimicrobial Potential of a Novel Phage-Derived Lytic Protein Against Pseudomonas aeruginosa

Abstract

The escalation of bacterial resistance to existing antibiotics represents a growing global health challenge, exacerbated by the widespread misuse of antimicrobial agents. As a result, alternative antibacterial strategies are increasingly being explored, including phage-derived lytic proteins. In this study, we report a preliminary characterisation of a novel phage-derived lytic protein identified through computational screening of bacteriophage genome sequences. A putative open reading frame, designated SM07 (1383 bp), was selected from bacteriophage sequences contributed by the University of KwaZulu-Natal to a global phage repository. The gene was synthesised, sub-cloned into the pET-30b(+) vector with an N-terminal histidine tag, and recombinantly expressed in <i>Escherichia coli</i> BL-21(AI) cells. The protein was purified using affinity and ion-exchange chromatography. Purified SM07 exhibited in vitro antimicrobial activity against <i>Pseudomonas aeruginosa</i>, with a minimum inhibitory concentration of 4 µg/mL, while no significant cytotoxic effects were observed in Vero kidney cells at concentrations substantially above the effective dose. Together, these findings provide initial evidence supporting the antimicrobial potential of SM07 and highlight phage-derived lytic proteins as candidates for further investigation as alternative agents against <i>P. aeruginosa</i>-associated infections.