Engineered gram-negative endolysins

The polypeptide according to any one of the preceding claims, wherein the globular endolysin is a endopeptidase, chitinase, T4 like muraminidase, lambda like muraminidase, N-acetyl-muramoyl-L-alanine-amidase, muramoyl-L-alanine-amidase, muramidase, lytic transglycosylase (C), lytic transglycosylase (M), N-acetyl-muramidase, N-acetyl-glucosaminidase or transglycosylase.

The polypeptide according to any one of the preceding claims, wherein the globular endolysin is an endolysin deriving from a bacteriophage infecting bacteria of the genus selected from the group consisting of:

• Acinetobacter, Aeromonas, Aggregatibacter, Azospirillum, Bacteroides, Burkholderia, Campylobacter, Candidatus, Caulobacter, Clavibacter, Cronobacter, Delftia, Enterobacter, Erwinia, Escherichia, Flavobacterium, Haemophilus, Iodobacteria, Klebsiella, Kluyvera, Mannheimia, Morganella, Neisseria, Pantoea, Pasteurella, Planktothrix, Pseudoalteromonas, Pseudomonas, Ralstonia, Salmonella, Shigella, Sinorhizobium, Sodalis, Synechococcus, Thalassomonas, Thermus, Vibrio, Xanthomonas, Xylella, and Yersinia.

The polypeptide according to any one of the preceding claims, wherein the globular endolysin is deriving from the group of endolysins listed in table 1.

The polypeptide according to any one of the preceding claims, wherein the polypeptide comprises an amino acid sequence selected from the group of sequences consisting of SEQ ID Nos.:

• 18, 19, 20, 21, 22, 23, 24, 25, 27 and 28.

The polypeptide according to any one of the preceding claims, wherein the polypeptide does not comprise the amino acid sequence of a Gram-negative modular endolysin.

The polypeptide according to any one of the preceding claims, wherein the polypeptide does not comprise an enzymatically active domain (EAD) of a Gram-negative modular endolysin.

The polypeptide according to any one of the preceding claims, wherein the enzymatic activity of the globular endolysin is the only enzymatic activity of the polypeptide.

The polypeptide according to any one of the preceding claims, wherein the amino acid sequence of the globular endolysin exhibits less than 90% sequence identity with the amino acid sequence of an enzymatically active domain of any modular endolysin.

The polypeptide according to any one of the preceding claims, wherein the amino acid sequence of the globular endolysin and the amino acid sequence of the cell wall binding domain are either linked directly to each other or via an intermediate linker sequence, the linker sequence preferably not exceeding more than 50 amino acids in length.

The polypeptide according to any one of the preceding claims, wherein the polypeptide degrades peptidoglycan of at least one Gram-negative bacterial species.

The polypeptide according to any one of the preceding claims, wherein the polypeptide binds to peptidoglycan of at least one Gram-negative bacterial species.

The polypeptide according to any one of the preceding claims wherein the polypeptide comprises an amino acid sequence selected from the group of sequences consisting of SEQ ID NOs:

• 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 and 40, wherein SEQ ID NO:
• 40 is preferred.

The polypeptide according to any one of the preceding claims, wherein the polypeptide comprises additionally at least one amino acid sequence selected from the group consisting of amphipathic peptide, cationic peptide, polycationic peptide, hydrophobic peptide, naturally occurring antimicrobial peptide, sushi peptide and defensin.

The polypeptide according to any one of the preceding claims, wherein the polypeptide comprises additionally a tag sequence.