Antibiotic-resistant bacteria are an urgent global health crisis that threatens to surpass cancer as a cause of death within 20-30 years. Streptococcus pneumoniae (the pneumococcus), a priority pathogen according to the World Health Organization (WHO), causes serious infections such as pneumonia and meningitis, for which current antibiotics are often ineffective and can release toxins that damage nerve tissue. This project is developing innovative 'dual-function' endolysins that both kill resistant bacteria and neutralize their toxins. By combining CPL-1 and CPL-7S endolysins with peptides that bind pneumolysin, the primary cytotoxin, we can treat infections even in the central nervous system. The constructs also break down biofilms and protect neurons from toxin-induced damage. Early results show that our endolysins can cross the blood-brain barrier, eliminate S. pneumoniae and neutralize pneumolysin. The project integrates protein engineering, cellular models and animal studies to develop a novel therapeutic platform with the potential to greatly reduce the health and socio-economic burden of antibiotic-resistant infections.