METHOD AND COMPOSITION USING A DUAL SPECIFICITY PROTEIN TYROSINE PHOSPHATASE AS AN ANTIMALARIAL DRUG TARGET
Phosphotyrosine phosphatase (PTP) encoded by PF13_0027 is a desirable drug target for the human malaria parasite Plasmodium falciparum . This PTP is critical for intraerythrocytic parasite development and invasion of erythrocytes by malaria merozoites. Mutation of the PF13_0027 gene or blocking expression of PTP function to create a PTP-null parasite severely attenuates the malaria parasite's ability to survive, making the PTP-null parasite suitable as an attenuated blood-stage parasite vaccine.
1 . A method of treating malaria comprising contacting a cell infected with a Plasmodium species with a therapeutically effective amount of a phosphatase inhibitor.
2 . The method of claim 1 wherein the cell is selected from the group consisting of erythrocytes and hepatocytes.
3 . The method of claim 1 wherein the phosphatase inhibitor is selected from the group consisting of CDC25 phosphatase inhibitors and dual specificity protein tyrosine phosphatase inhibitors.
4 . The method of claim 1 wherein the phosphatase inhibitor targets a protein gene in a Plasmodium species wherein the protein has an amino acid sequence having homology to SEQ ID NO: 1.
5 . The method of claim 1 wherein the Plasmodium species is selected from the group consisting of P. falciparum and P. vivax.
6 . A method of preventing malaria comprising regulating the cell cycle of a Plasmodium species by inhibiting the expression of the P13 — 0027 protein.
7 . The method of claim 6 wherein the Plasmodium species is selected from the group consisting of P. falciparum and P. vivax.
8 . The method of claim 6 wherein the P13 — 0027 protein has an amino acid sequence having homology to SEQ ID NO: 1.
9 . The method of claim 6 wherein the expression of the P13 — 0027 protein is inhibited by a phosphatase inhibitor.
10 . The method of claim 9 wherein the phosphatase inhibitor is selected from the group consisting of CDC25 phosphatase inhibitors and dual specificity protein tyrosine phosphatase inhibitors.
11 . A method of preventing malaria comprising regulating the cell cycle of a Plasmodium species by inhibiting the expression of the P13 — 0027 gene.
12 . The method of claim 11 wherein the Plasmodium species is selected from the group consisting of P. falciparum and P. vivax
13 . The method of claim 11 wherein the expression of P13 — 0027 is inhibited by the insertion of a genetic element in the open reading frame.
14 . The method of claim 13 wherein the genetic element is selected from the group consisting of nucleic acids and transposon sequences.
15 . The method of claim 13 wherein the genetic element is inserted into a TTAA sequence in the open reading frame.
16 . A method of preventing malaria comprising administering a therapeutically effective amount of a PTP-null Plasmodium species and a pharmaceutically acceptable carrier.
17 . The method of claim 16 wherein the PTP-null Plasmodium species has the insertion of a genetic element in the open reading frame.
18 . The method of claim 17 wherein the genetic element is selected from the group consisting of nucleic acids and transposon sequences.
19 . The method of claim 17 wherein the genetic element is inserted into a TTAA sequence in the open reading frame.
20 . A pharmaceutical composition for preventing malaria comprising a PTP-null Plasmodium species and a pharmaceutically acceptable carrier.
21 . The composition of claim 20 wherein the PTP-null Plasmodium species has the insertion of a genetic element in the open reading frame.
22 . The composition of claim 21 wherein the genetic element is selected from the group consisting of nucleic acids and transposon sequences.
23 . The composition of claim 21 wherein the genetic element is inserted at a TTAA sequence in the open reading frame.