Development of Novel Chimeric Endolysin Conjugated with Chitosan-Zn-Metal–Organic Framework Nanocomposites with Antibacterial Activity

Bacterial diseases have been considered the most crucial issue and are threatening human health all around the world. Also, resistance to antimicrobial drugs has become a big hurdle against efficient therapy. As a result, recombinant chimeric endolysin was produced in E. coli host to use as a potential antibacterial agent against bacteria resistance and replacement to conventional antibiotics in this study. Then, chitosan (C)–coated nanoscale metal–organic frameworks (CS-NMOFs) nanocomposite was synthesized as a novel nano delivery system to further improve the antibacterial activity of endolysin. After characterization of nanocomposite with analytical devices such as FT-IR, DLS, and TEM and determining the nanometric size of samples (30 nm to 90 nm), endolysin was covalently (endolysin-CS-NMOFs (C)) and non-covalently (endolysin-CS-NMOFs (NC)) conjugated to nanocomposite. Thereafter, the lytic ability, synergistic interaction, and biofilm reduction manner of endolysin-containing CS-NMOF nanocomposites were evaluated on E. coli, S. aureus, and P. aeruginosa strains. The results depicted an excellent lytic ability of nanocomposites after 24 h and 48 h of treatment, especially endolysin-CS-NMOFs (NC) on E. coli and P. aeruginosa strains. The synergistic interaction between nanocomposite and vancomycin did not attain for P. aeruginosa strain whereas the reverse was true for E. coli and S. aureus strains at 8 ng/mL concentration. Next, nanocomposites demonstrated potential biofilm reduction activities in various strains, especially in S. aureus and P. aeruginosa. Ultimately, our outputs demonstrate an efficient performance of the synthesized nanocomposite as an appropriate substitution for conventional antibiotics against bacteria. Graphical abstract: (Figure presented.)