Genetic and epigenetic manipulation of ABC transporters and ecto-phosphatases for the conference of drug resistance and for the loss of drug resistance in biological systems and methods for the detection of ecto-phosphatase inhibitors

A method of altering the ATP gradient across the biological membrane of a target bacteria, yeast, plant or mammalian cell to achieve an increase in drug resistance comprising up-regulating an ecto-phosphatase in the target cell.

A method for altering the ATP gradient across the biological membrane of a target bacteria, yeast, plant or mammalian cell to achieve a decrease in drug resistance comprising down-regulating an ecto-phosphatase in a target cell.

A method for altering the ATP gradient across the biological membrane of a plant cell to achieve an increase in drug resistance comprising up-regulating an ABC transporter in the target cell.

A method for altering the ATP gradient across the biological membrane of a plant cell to achieve a decrease in drug resistance comprising down-regulating an ABC transporter in the target cell.

A method for augmenting the chemotherapeutic effectiveness of a chemotherapeutic molecule by decreasing resistance to the chemotherapeutic molecule in a target cell comprising down-regulating an ecto-phosphatase in a target cell.

A method for conferring herbicide resistance to a plant comprising up-regulating an ecto-phosphatase in the target cell.

A method for increasing sensitivity to a drug molecule to inhibit or ameliorate microorganism infection in animals and humans by altering the ATP gradient across the biological membrane of a microorganism to achieve a decrease in drug resistance comprising down-regulating an ecto-phosphatase in a target cell.

A method for inhibiting an ecto-phosphatase comprising contacting an ecto-phosphatase with an ecto-phosphatase inhibiting amount of an ecto-phosphatase inhibitor selected from the group consisting of molecules having the Formulae I through XIX:

• 2

The method of claim wherein the ecto-phosphatase is selected from the group consisting of Pisum sativum apyrase (GenBank accession # Z32743) and Homo sapiens apyrases (GenBank accession #AF 034840, AF0399ecto-phosphatase, AF039917, AF039918 and HSU87967).

A method for decreasing drug resistance in a target bacteria, yeast, plant or mammalian cell comprising introducing to cells a drug resistance-inhibiting amount of an ecto-phosphatase inhibitory molecule selected from the group consisting of molecules having the Formulae I through XIX:

• 5

A method of identifying an inhibitor of an ecto-phosphatase comprising

• a) contacting the ecto-phosphatase with a small molecule in the presence of ATP under conditions wherein the ecto-phosphatase has ATPase activity,
• b) incubating the ecto-phosphatase, small molecule and ATP for a period of time sufficient to liberate phosphate from the ATP, and
• c) adding ammonium molybdate and ascorbic acid to the ecto-phosphatase, small molecule and ATP to form a complex with liberated phosphate and to generate a dark blue color, wherein inhibition of the ecto-phosphatase by the small molecule results in less phosphate liberated and less blue color.