Cecropin A-Derived Peptide for the Treatment of Osteomyelitis by Inhibiting the Growth of Multidrug-Resistant Bacteria and Eliminating Inflammation
Ziao Zhou, Peng Zhang, Dinghao Chen, Nan Kong, Huayang Liu, Juan Boo Liang, Kai Huang, Huaimin Wang
Abstract
Osteomyelitis poses substantial therapeutic challenges due to the prevalence of multidrug-resistant bacterial infections and associated inflammation. Current treatment regimens often rely on a combination of corticosteroids and antibiotics, which can lead to complications and impede effective bacterial clearance. In this study, we present CADP-10, a Cecropin A-derived peptide, designed to target methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MRE), while simultaneously addressing inflammatory responses. CADP-10 self-assembles into nanobacterial net (NBacN) that selectively identify and bind to bacterial endotoxins (LPS and LTA), disrupting membrane integrity and depolarizing membrane potential, which culminates in bacterial death. Importantly, these NBacN are bound to LPS and LTA from dead bacteria, preventing their engagement with TLR receptors and effectively blocking downstream inflammatory pathways. Our assessments of CADP-10 demonstrate good biosafety in both in vitro and in vivo models. Notably, in a rabbit osteomyelitis model, CADP-10 eliminated MRSA-induced bone infections, mitigated inflammation, and promoted bone tissue regeneration. This research highlights the potential of CADP-10 as a multifunctional antimicrobial agent for the management of infectious inflammatory diseases.