METHODS FOR TREATING GRAM POSITIVE BACTERIAL INFECTION
The present invention relies on the discovery that, surprisingly, when it is produced locally in the epidermis, hepcidin is able to directly initiate the recruitment of neutrophils by increasing the CXCL1 production in keratinocytes. While hepcidin had no direct antimicrobial activity against Group A Streptococcus (GAS), injection of hepcidin, at the site of infection prevented GAS systemic spread. Hepcidin agonists may represent a novel therapeutic to prevent life threatening bacteremia not only in streptococcal NF but also in complicated infections due to compromised host immunity. The present invention relates to a method for treating Gram-positive bacterial infection in a patient in need thereof, comprising administering to the patient hepcidin polypeptide. More specifically, it concerns method for treating with mature form of hepcidin, gram-positive bacterial infection such as Group A Streptococcus infection which could be associated with Necrotizing fasciitis (NF).
1 . Method for treating a Gram positive bacterial infection in a patient in need thereof, comprising administering to the patient
a polypeptide comprising a sequence of 20 amino acids having
at least 50% identity or at least 60% identity with the sequence SEQ ID NO: 1, and
cysteine residues at positions 2, 5, 6, 8, 9, 14, 17, and 18;
or
a nucleic acid encoding said polypeptide.
2 . The method according to claim 1 , wherein said polypeptide is a vertebrate homologue of a mature form of human hepcidin.
3 . The method according to claim 2 wherein said vertebrate homologue is a mammalian homologue.
4 . The method according to claim 1 , wherein the polypeptide is a polypeptide of 25 amino-acids having the sequence SEQ ID NO: 3.
5 . The method according to claim 1 , wherein the Gram positive bacterial infection is caused by a gram positive bacteria that is a hyperinvasive bacteria.
6 . The method according to claim 1 , wherein the gram positive bacteria is selected from the group consisting of Streptococcus, Staphylococcus, Clostridium, Listeria, Bacillus and Corynebacterium.
7 . The method according to claim 6 wherein the gram positive bacteria is a Streptococcus selected from the group consisting of a beta-hemolytic Streptococcus , an alpha hemolytic Streptococcus and a gamma haemolytic Streptococcus.
8 . The method according to claim 7 wherein the gram positive bacteria is a Group A beta-hemolytic Streptococcus (GAS).
9 . The method according to claim 1 , wherein the Gram positive bacterial infection is associated with Necrotizing fasciitis (NF).
10 . The method of claim 7 , wherein the beta-hemolytic Streptococcus is a Group B beta-hemolytic Streptococcus.