Bacteriophages producing heterologous bacteriocins
The present invention relates to the field of medicine, specifically the field of bacterial infection and treatment thereof.
1 . A modified bacteriophage capable of infecting a host bacterium, wherein the bacteriophage genome comprises a gene that is foreign to the bacteriophage, wherein said gene encodes a bacteriocin selected from the group consisting of Colicin M as set forth in SEQ ID NO: 18, Colicin E7 as set forth in SEQ ID NO: 20, Colicin K as set forth in SEQ ID NO: 19, Colicin 5 as set forth in SEQ ID NO: 17, Colicin E6 as set forth in SEQ ID NO: 16 and Klebicin M as set forth in SEQ ID NO: 21, while maintaining its wild-type bacteriocin functionality.
2 . The modified bacteriophage according to claim 1 , wherein the host bacterium is selected from the group consisting of: Acetinobacter, Chronobacter, Bortadella, Burkholderia, Campylobacter, Staphylococcus, Pneumococcus, Enterococcus, Klebsiella, Escherichia, Pseudomonas, Salmonella, Shigella, Vibrio, Neisseria, Brucella, Haemophilus, Mycobacterium, Listeria, Legionella, Yersinia, Chlamydia, Clostridium, Helicobacter, Corynebacterium, Lactobacillus, Fusobacterium , and Streptococcus.
3 . The modified bacteriophage according to claim 1 , wherein the host bacterium is an Escherichia coli ( E. coli ) species and wherein the bacteriocin targets said E. coli species, or wherein the host bacterium is an E. coli species and wherein the bacteriocin does not target said E. coli species.
4 . The modified bacteriophage according to claim 1 , wherein the host bacterium is an Enterococcus species, and wherein the bacteriocin targets said Enterococcus species, or wherein the host bacterium is an Enterococcus species, and wherein the bacteriocin does not target said Enterococcus species.
5 . The modified bacteriophage according to claim 1 , wherein the host bacterium is a Klebsiella species, and wherein the bacteriocin targets said Klebsiella species or wherein the host bacterium is a Klebsiella species, and wherein the bacteriocin does not target said Klebsiella species.
6 . The modified bacteriophage according to claim 1 , wherein the bacteriophage is derived from wild-type bacteriophage Klebsiella phage K1, E. coli phage CM001, E. coli phage E2, Enterococcus phage Efs3, Enterococcus phage Efs7 or from E. coli phage phi41S.
7 . A composition comprising a carrier and the modified bacteriophage as defined in claim 1 .
8 . The composition according to claim 7 , wherein the composition is a pharmaceutical composition.
9 . The modified bacteriophage according to claim 1 , wherein the bacteriocin targets species of the host bacterium, or wherein the bacteriocin does not target species of the host bacterium.
10 . The modified bacteriophage according to claim 4 , wherein the Enterococcus species is Enterococcus faecalis.
11 . The modified bacteriophage according to claim 5 , wherein the Klebsiella species is Klebsiella pneumoniae.
12 . The pharmaceutical composition according to claim 8 , wherein the pharmaceutical composition is formulated for topical, intravenous, intramuscular, intrathecal, oral, intraperitoneal, vaginal, rectal, lumbar, or meningeal administration.
13 . A method of treatment of a bacterial infection in a subject in need thereof comprising administration of the modified bacteriophage according to claim 1 to the subject.