Project Title: Molecular design of DNA phage-derived endolysins for targeting Gram-negative bacteria

Project No: lzp-2021/1-0050

Period: 1 January 2022 – 31 December 2024

Project costs: 299999,70 EUR

Principle Investigator: Dr.biol. Tatjana Kazāka

Summary

The increasing prevalence of multidrug-resistant bacteria calls for an urgent need to develop alternatives to conventional antibiotics. A promising new class of antibacterials are endolysins, the enzymes which bacterial viruses (phages) use to degrade the peptidoglycan layer in the bacterial cell wall, resulting in lysis and cell death. While endolysins are highly potent against Gram-positive bacteria, the presence of an outer membrane in Gram-negative bacteria hinders their more widespread use. The proposed project will focus on modified endolysins designed to facilitate their passage through the outer membrane of Gram-negative bacteria and leading to cell lysis. The project will comprise detailed studies on the lytic potential of (i) a novel type of globular endolysin from the Chivirus-related phage Enc34 and (ii) five selected modular endolysins from E. coli phages. Functional studies of these proteins will involve their fusion with different antimicrobial peptides to generate novel lytic agents with a broad-spectrum activity. The resulting engineered endolysins are expected to have considerable potential against such Gram-negative pathogens as multidrug-resistant Salmonella, Klebsiella, Psudomonas and others.

Information published 03.01.2022.