Engineered lysines as an innovative antimicrobial strategy for the treatment of coliform mastitis Mastitis, an infection of the udder in cows, is often caused by gram-negative Escherichia coli (E. coli). Severe mastitis is frequently treated with 3rd and 4th generation cephalosporins and there is an increasing prevalence of antibiotic resistance. Those strains, including E.
coli producing β-lactamase are recognized by WHO as priority pathogens and these cephalosporins are critical drugs that should be reserved for humans. Thus, there is an urgent need for alternative antimicrobial agents to treat mastitis.
Bacteriophage-derived lysines are novel and sustainable enzyme-based antibiotics with high efficiency and specificity. Until recently, the lysine strategy against gram-negative bacteria failed due to the lipopolysaccharide outer membrane preventing access to the inner peptidoglycan layer. Therefore, in this project lysines will be engineered against gram-negative bacteria that cause coliform mastitis. After production and purification of this new generation of lysines, their efficacy and safety of these lysines will be assessed in vitro and in vivo to provide a proof-of-concept.