Antimicrobial agents

Inventors

Lavigne, Rob • Miller, Stefan • Briers, Yves • Volckaert, Guido • Walmagh, Maarten

Abstract

The application relates to antimicrobial agents against Gram-negative bacteria, in particular to fusion proteins composed of an enzyme having the activity of degrading the cell wall of Gram-negative bacteria and a peptide stretch fused to the enzyme at the N- or C-terminus, as well as pharmaceutical compositions comprising the same. Moreover, it relates to nucleic acid molecules encoding such a fusion protein, vectors comprising said nucleic acid molecules and host cells comprising either said nucleic acid molecules or said vectors. In addition, it relates to such a fusion protein for use as a medicament, in particular for the treatment or prevention of Gram-negative bacterial infections, as diagnostic means or as cosmetic substance. The application also relates to the treatment or prevention of Gram-negative bacterial contamination of foodstuff, of food processing equipment, of food processing plants, of surfaces coming into contact with foodstuff, of medical devices, of surfaces in hospitals and surgeries.

Core Innovation

The invention relates to antimicrobial fusion proteins against Gram-negative bacteria. The fusion protein includes an endolysin, or related lytic enzyme, having the activity of degrading the cell wall of Gram-negative bacteria, and a peptide segment fused to the endolysin at the N-terminus and/or C-terminus. The peptide segment is provided in specific peptide classes and includes peptides such as cathelicidine LL-37 and magainin peptides, including magainin II.

The disclosed fusion design centers on attaching a peptide segment to an endolysin to create a single fusion protein comprising an endolysin and a peptide segment fused at the N-terminus or C-terminus or both termini. The peptide segment is described as a cathelicidine or a magainine, and embodiments are provided where the peptide segment is defined by a specific sequence identity, including “where the peptide segment comprises SEQ ID NO: 33.”

Embodiments further describe the endolysin fusion constructs as including nucleic acids, vectors, and host cells encoding or containing the fusion proteins. The document also describes pharmaceutical, cosmetic, and diagnostic uses, and decontamination use settings for surfaces and devices, and for food-related contexts, as well as antimicrobial activity testing against panels of Gram-negative strains.

Claims Coverage

The partial claims set includes two independent claims. They cover inventive features centered on fusing an endolysin that degrades Gram-negative bacterial cell walls to a cathelicidine or magainine peptide segment at the N- and/or C-terminus, including a specific sequence-defined peptide segment in a second independent claim.

Across the independent claims, the core claim coverage is the terminal fusion of an endolysin active against Gram-negative bacteria with a peptide segment that is either a cathelicidine/magainine or is defined by a specific sequence identity (SEQ ID NO: 33).

Stated Advantages

Documented Applications