Project: Burnzymes

2019-01-01 – 2022-12-31

Abstract

As multidrug-resistant organisms fail to respond to currently available antimicrobial therapy,
infections become more severe and cause more complications. Especially vulnerable to infections
are burn wounds patients. Staphylococcus aureus (Gram-positive bacterium), an early burn wound
colonizer, as well as Pseudomonas aeruginosa and Acinetobacter baumannii (Gram-negative
bacteria) are known to be the most dangerous and life-threating wound pathogens.
(Engineered) endolysins are a novel class of enzyme-based antibiotics (enzybiotics) which have
currently progressed to phase II clinical trials. A unique feature of enzybiotics is their modular
composition which can be engineered to modulate their specificity and antibacterial properties. We
have recently developed a set of complementary techniques to design, analyze and select modular
enzybiotics in a highly efficient way. This has yielded initial enzybiotic variants with high efficacy in
serum, high stability and specificity for the three burn wound pathogens.
Our innovative approach will allow for the first time to design a new type of enzybiotics, called
Burnzymes, that will act not only against the three main burn wound pathogens, but also improve
the burn wound healing process. We will therefore expand the current modular enzybiotics with
additional modules such as specific peptides with antibacterial/anti-biofilm/antiinflammatory/
wound healing properties and the recently discovered, phage-encoded mini Dnases