Polycationic nanopeptide-fused endolysins for the control of Mannheimia haemolytica

reductions of up to 4.5 in bacterial counts across M. haemolytica serotypes, particularly when combined with EDTA which increased permeability of the OM. These findings highlight the synergistic potential of engineered endolysins and EDTA in overcoming the gram-negative barrier. Additionally, selecting an appropriate buffer was found crucial to rule out the effect of buffers on antibacterial activity of endolysins. To our knowledge, this is the first report of engineering and evaluating prophage-derived endolysins against M. haemolytica, underscoring their promise as innovative therapeutics for BRD. KEY POINTS: • Prophage endolysins are potent antibacterials with engineering potential. • Chelator synergy boosts endolysin efficacy; buffer choice is critical. • Endolysins hold strong promise as next-generation therapeutic agents against multi-drug-resistant M. haemolytica causing bovine respiratory disease.