Engineered endolysins to fight antibiotic-resistant streptococcal infections and neutralize toxins

Streptococcal infections are important contributors to human disease, including Streptococcus pneumoniae (the pneumococcus) as the major cause of bacterial pneumonia and meningitis globally, and Streptococcus pyogenes (group A streptococcus; GAS) as important cause of septic shock and necrotizing soft tissue infections in adults and children.

Based on the noted increased antimicrobial resistance, including also multi-drug resistance, Centers for Disease Control and Prevention recently listed S. pneumoniae and GAS as serious and concerning antibiotic resistance threats, respectively.New antibiotics can be discovered, however bacteria’s unique ability to adapt to the environment leads to resistance.

It is predicted that by year 2050 the deaths attributed to antibiotic-resistant infections will reach 10 million deaths per year, overpassing any other major death-causing disease that we have today.Endolysins, phage-derived peptidoglycan hydrolases that break down Gram-positive bacterial cell walls, are promising alternative treatments due to their rapid mode of action, high specificity for targeting bacteria, and low probability of resistance development.

In this project, endolysins targeting S. pneumoniae and GAS will be engineered.

The novel endolysin versions will be constructed to have antimicrobial activity and, simultaneously, bind and neutralize the cytotoxins released by the bacteria thereby limiting tissue pathology, achieving what current antibiotics cannot do.