Medicament for lct poisoning

Abstract

The medicament for the prevention or the relief of poisoning by large clostridial cytotoxins (LCTs), in particular Clostridium difficile toxins A and B (TcdA and TcdB), is characterized by containing as active ingredient at least one effector, namely an inhibitor or activator of the autocatalytic protease activity of LCTs (large clostridial cytotoxins).

1 . Medicament for prevention or relief of poisoning by LCT (=large clostridial cytotoxins), comprising, as active ingredient at least one effector, wherein said at least one effector is an inhibitor or activator of a protease activity of said LCT. 
     
     
         2 . Medicament according to  claim 1 , wherein said at least one effector is an inhibitor or activator of a protease activity of  Clostridium difficile  toxin A (TcdA) and/or  Clostridium difficile  toxin B (TcdB) and/or  Clostridium sordellii  lethal toxin (TcsL) and/or  Clostridium novyi  α-toxin (Tcnα). 
     
     
         3 . Medicament according to  claim 1 , wherein the inhibitor is 1,2-epoxy-3-(p-nitrophenoxy)-propane (EPNP). 
     
     
         4 . Medicament according to  claim 3 , wherein the activator is an inositol phosphate, preferably inositol hexaphosphate (IP6). 
     
     
         5 . Medicament according to  claim 1 , wherein the effector is a competitively inhibiting structural analogue of inositol phosphate, preferably inositol hexaphosphate (IP6). 
     
     
         6 . Medicament according to  claim 1 , wherein the activator is a substance which analogous to IP6 promotes (autocatalytic) protease activity of LCTs, in particular of TcdA and/or TcdB and/or TcsL and/or Tcnα. 
     
     
         7 . Medicament according to  claim 1 , wherein the effector is a chemical substance that reduces inositol phosphate concentration in gut lumen of mammals, in particular humans. 
     
     
         8 . Medicament according to  claim 1 , wherein the effector is a chemical substance that reduces inositol phosphate concentration in mammalian cells, in particular human cells. 
     
     
         9 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody, which interacts with an active centre of the protease in TcdB protein region of AS 1500 to AS 1800 according to TcdB amino acid sequence No. P18177 (SwissProt/TrEMBL). 
     
     
         10 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with TcdB protein region of AS 1653 to AS 1678 according to TcdB amino acid sequence No. P18177 (SwissProt/TrEMBL). 
     
     
         11 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody, which interacts with the DXG motif at amino acid position AS 1665 of the TcdB protein according to TcdB amino acid sequence No. P18177 (SwissProt/TrEMBL). 
     
     
         12 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with TcdA protein region of AS 1651 to AS 1675 according to TcdA amino acid sequence No. P16154 (SwissProt/TrEMBL). 
     
     
         13 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with a DXG motif at amino acid position AS 1662 of a TcdA protein according to TcdA amino acid sequence No. P16154 (SwissProt/TrEMBL). 
     
     
         14 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with TcsL protein region of AS 1654 to AS 1679 according to TcsL amino acid sequence No Q46342 (SwissProt/TrEMBL). 
     
     
         15 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with a DXG motif at amino acid position AS 1666 of a TcsL protein according to TcsL amino acid sequence No. Q46342 (SwissProt/TrEMBL). 
     
     
         16 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with a Tcnα protein region of AS 1641 to AS 1665 according to Tcnα amino acid sequence No Q46149 (SwissProt/TrEMBL). 
     
     
         17 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with a TcdB protein region of AS 1400 to AS 2300 according to TcdB amino acid sequence No. P18177 (SwissProt/TrEMBL) or with protein regions of TcdA or TcsL or Tcnα equivalent or homologous thereto. 
     
     
         18 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with a TcdB protein region of AS 1517 to AS 2142 according to TcdB amino acid sequence No. P18177 (SwissProt/TrEMBL) or with protein regions of TcdA or TcsL or Tcnα equivalent or homologous thereto. 
     
     
         19 . Medicament according to  claim 1 , wherein the inhibitor is a chemical substance, in particular a protein, more particularly an antibody which interacts with a TcdB protein region of AS 1517 to AS 1593 or of AS 1918 to AS 2142 according to TcdB amino acid sequence No. P18177 (SwissProt/TrEMBL) or with protein regions of TcdA or TcsL or Tcnα equivalent or homologous thereto. 
     
     
         20 . Medicament for prevention or relief of poisoning by LCT (=large clostridial cytotoxins), wherein the medicament
 (1.) is suited for administration as a vaccine and   (2.) as an antigen active ingredient
 (a) contains a TcdB protein fragment of TcdB amino acid sequence No. P18177 (SwissProt/TrEMBL) which comprises at least a DXG motif at position 1665, preferably an amino acid sequence of amino acid positions AS 1653 to AS 1678 and more preferably an amino acid sequence of amino acid positions AS 1500 to AS 1800, 
 and/or (b) contains a TcdA protein fragment of TcdA amino acid sequence No. P16154 (SwissProt/TrEMBL), which comprises at least a DXG motif at position 1662, preferably an amino acid sequence of amino acid positions AS 1651 to AS 1675, 
 and/or (c) contains a TcsL protein fragment of TcsL amino acid sequence No. Q46342 (SwissProt/TrEMBL), which comprises at least a DXG motif at position 1666, preferably an amino acid sequence of amino acid positions AS 1654 to AS 1679, 
 and/or (d) contains a Tcnα protein fragment of Tcnα amino acid sequence No. Q46149 (SwissProt/TrEMBL), which comprises at least an amino acid sequence of AS 1641 to AS 1665.