PIRIN POLYPEPTIDE AND IMMUNE MODULATION
The present invention relates to polypeptide HP, or a polynucleotide sequence encoding polypeptide HP, or a host cell comprising said polynucleotide sequence, or a host cell comprising an expression vector comprising said polynucleotide sequence, for use in the treatment and/or prevention of a disorder in a subject; wherein said disorder is an inflammatory disorder and/or an autoimmune disorder; wherein said polypeptide has at least 75% identity to SEQ ID NO 2, SEQ ID NO 4 or SEQ ID NO 6 or variants, homologues, fragments or derivatives thereof; and wherein said polynucleotide sequence encodes a polypeptide which has at least 75% identity to SEQ ID NO 2, SEQ ID NO 4 or SEQ ID NO 6 or variants, homologues, fragments or derivatives thereof and/or wherein said polynucleotide sequence has at least 75% identity to SEQ ID NO 1, SEQ ID NO 3 or SEQ ID NO 5 or variants, homologues, fragments or derivatives thereof.
1 .- 71 . (canceled)
72 . A method of preventing infection by one or more bacteria or reducing a level of the one or more bacteria in a tissue or an organ in a subject, comprising administering to the subject a pharmaceutical composition that comprises:
(i) a pirin-related polypeptide of Bacteroides thetaiotaomicron , wherein the pirin-related polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 2, as determined by a sequence alignment performed using a Basic Local Alignment Search Tool algorithm with a gap open penalty of 0, a gap extension penalty of 0, and a Blocks Substitution Matrix of 62; and
(ii) a pharmaceutically acceptable excipient, diluent, or carrier.
73 . The method of claim 72 , wherein the subject has, or is at risk of developing, loss of gut barrier integrity.
74 . The method of claim 72 , wherein the one or more bacteria comprise one or more types of lactose fermenting bacteria, and wherein a level of the one or more types of lactose fermenting bacteria in the tissue or the organ of the subject is reduced.
75 . The method of claim 72 , wherein the one or more bacteria comprise one or more types of non-lactose fermenting bacteria, and wherein a level of the one or more types of non-lactose fermenting bacteria in the tissue or the organ of the subject is reduced.
76 . The method of claim 72 , wherein the tissue is selected from the group consisting of a mesenteric lymph node, a liver, and a spleen.
77 . The method of claim 72 , wherein the administering improves the subject's gut barrier integrity as compared to prior to the administering.
78 . The method of claim 74 , wherein the one or more types of lactose fermenting bacteria comprise E. coli, Enterobacter , or Klebsiella.
79 . The method of claim 75 , wherein the one or more types of non-lactose fermenting bacteria comprise Salmonella, Proteus, Pseudomonas aeruginosa , or Shigella.
80 . The method of claim 72 , wherein the pharmaceutical composition is a solid composition.
81 . The method of claim 72 , wherein the pharmaceutical composition is a liquid composition.
82 . The method of claim 72 , wherein the pirin-related polypeptide is encapsulated in a capsule.
83 . The method of claim 82 , wherein the capsule is an enterically resistant capsule for delivery to an intestine of the subject.
84 . The method of claim 72 , wherein the pirin-related polypeptide is Polypeptide Hypothetical Protein (HP).
85 . The method of claim 72 , wherein the administering is oral, parenteral, intramuscular, intraperitoneal, subcutaneous, intradermal, or intravenous.
86 . The method of claim 72 , wherein the pirin-related polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 2, as determined by a sequence alignment performed using a Basic Local Alignment Search Tool algorithm with a gap open penalty of 0, a gap extension penalty of 0, and a Blocks Substitution Matrix of 62.
87 . A method of regulating the expression of one or more pro-inflammatory genes or barrier integrity genes in a cell or cells of a subject, comprising administering to the subject a pharmaceutical composition that comprises:
(i) a pirin-related polypeptide of Bacteroides thetaiotaomicron , wherein the pirin-related polypeptide comprises an amino acid sequence having at least 90% identity to SEQ ID NO: 2, as determined by a sequence alignment performed using a Basic Local Alignment Search Tool algorithm with a gap open penalty of 0, a gap extension penalty of 0, and a Blocks Substitution Matrix of 62; and
(ii) a pharmaceutically acceptable excipient, diluent, or carrier.
88 . The method of claim 87 , wherein the one or more pro-inflammatory genes or barrier integrity genes is selected from the group consisting of regenerating islet-derived 3 beta (Reg3b), resistin-like gamma (Retnlg), resistin-like beta (Retnlb), sucrase-isomaltase (Si), defensin alpha 24 (Defa24), hydroxysteroid 11-beta dehydrogenase 2 (Hsd11b2), hydroxysteroid (17-beta), dehydrogenase 2 (Hsd17b2), resistin-Like Molecule-beta (RELMb), nuclear receptor 1D1 (Nr1d1), and thyroid hormone receptor alpha (Thra).
89 . The method of claim 87 , wherein the administering decreases the expression level of a gene selected from the group consisting of Reg3b, Retnlg, Retnlb, Si, and Defa24, relative to the expression level of the gene prior to the administering.
90 . The method of claim 87 , wherein the pirin-related polypeptide is Polypeptide Hypothetical Protein (HP).
91 . The method of claim 87 , wherein the pirin-related polypeptide comprises an amino acid sequence having at least 95% identity to SEQ ID NO: 2, as determined by a sequence alignment performed using a Basic Local Alignment Search Tool algorithm with a gap open penalty of 0, a gap extension penalty of 0, and a Blocks Substitution Matrix of 62.