Methods for the identification of inhibitors of S-adenosylmethionine decarboxylase as antibiotics

A method for identifying a test compound as a candidate for an antibiotic, comprising:

• a) contacting a test compound with a polypeptide selected from the group consisting of:
• i) a polypeptide consisting essentially of SEQ ID NO:3;
• ii) a polypeptide having at least ten consecutive amino acids of SEQ ID NO:3;
• iii) a polypeptide having at least 50% sequence identity with SEQ ID NO:3 and at least 10% of the activity of SEQ ID NO:3;
• and
• iv) a polypeptide consisting of at least 50 amino acids having at least 50% sequence identity with SEQ ID NO:3 and at least 10% of the activity of SEQ ID NO:3;
• and
• b) detecting the presence and/or absence of binding between the test compound and the polypeptide, wherein binding indicates that the test compound is a candidate for an antibiotic.

A method for identifying a test compound as a candidate for an antibiotic, comprising:

• a) contacting an S-adenosylmethionine decarboxylase polypeptide with S-adenosyl-L-methionine in the presence and absence of a test compound or with (5-deoxy-5-adenosyl) (3-aminopropyl) methylsulfonium salt, and CO2 in the presence and absence of a test compound, wherein the S-adenosylmethionine decarboxylase polypeptide is selected from the group consisting of:
• i) a polypeptide having at least 50% sequence identity with SEQ ID NO:3 and at least 10% of the activity of SEQ ID NO:3,
• ii) a polypeptide consisting essentially of SEQ ID NO:3,
• iii) a polypeptide comprising at least 50 consecutive amino acids of SEQ ID NO:3 and having at least 10% of the activity of SEQ ID NO:3;
• and
• iv) a polypeptide consisting of at least 50 amino acids having at least 50% sequence identity with SEQ ID NO:3 and having at least 10% of the activity of SEQ ID NO:3;
• and
• b) determining a change in concentration for at least one of S-adenosyl-L-methionine, (5-deoxy-5-adenosyl) (3-aminopropyl) methylsulfonium salt, and/or CO2 in the presence and absence of the test compound, wherein a change in the concentration for any of S-adenosyl-L-methionine, (5-deoxy-5-adenosyl) (3-aminopropyl) methylsulfonium salt, and/or CO2 indicates that the test compound is a candidate for an antibiotic.

A method for identifying a test compound as a candidate for an antibiotic, comprising:

• a) providing a fungal organism having a first form of an S-adenosylmethionine decarboxylase;
• b) providing a fungal organism having a second form of the S-adenosylmethionine decarboxylase, wherein one of the first or the second form of the S-adenosylmethionine decarboxylase has at least 10% of the activity of SEQ ID NO:3;
• and
• c) determining the growth of the organism having the first form of the S-adenosylmethionine decarboxylase and the organism having the second form of the S-adenosylmethionine decarboxylase in the presence of a test compound,
• wherein a difference in growth between the two organisms in the presence of the test compound indicates that the test compound is a candidate for an antibiotic.

A method for identifying a test compound as a candidate for an antibiotic, comprising:

• a) providing a fungal organism having a first form of an S-adenosylmethionine decarboxylase;
• b) providing a fungal organism having a second form of the S-adenosylmethionine decarboxylase, wherein one of the first or the second form of the S-adenosylmethionine decarboxylase has at least 10% of the activity of SEQ ID NO:3;
• and
• c) determining the pathogenicity of the organism having the first form of the S-adensoylmethionine decarboxylase and the organism having the second form of the S-adenosylmethionine decarboxylase in the presence of a test compound,
• wherein a difference in pathogenicity between the two organisms in the presence of the test compound indicates that the test compound is a candidate for an antibiotic.

A method for identifying a test compound as a candidate for an antibiotic, comprising:

• a) providing a fungal organism having a first form of a gene in the polyamine biosynthetic pathway;
• b) providing a fungal organism having a second form of said gene in the polyamine biosynthetic pathway, wherein one of the first or the second form of the gene has at least 10% of the activity of a corresponding Magnaportha grisea gene;
• and
• c) determining the growth of the organism having the first form of the gene and the organism having the second form of the gene in the presence of a test compound,
• wherein a difference in growth between the two organisms in the presence of the test compound indicates that the test compound is a candidate for an antibiotic.

A method for identifying a test compound as a candidate for an antibiotic, comprising:

• a) providing a fungal organism having a first form of a gene in the polyamine biosynthetic pathway;
• b) providing a fungal organism having a second form of said gene in the polyamine biosynthetic pathway, wherein one of the first or the second form of the gene has at least 10% of the activity of a corresponding Magnaportha grisea gene;
• and
• c) determining the pathogenicity of the organism having the first form of the gene and the organism having the second form of the gene in the presence of a test compound,
• wherein a difference in pathogenicity between the organism and the comparison organism in the presence of the test compound indicates that the test compound is a candidate for an antibiotic.

A method for identifying a test compound as a candidate for an antibiotic, comprising:

• a) providing paired growth media containing a test compound, wherein the paired growth media comprise a first medium and a second medium and the second medium contains a higher level of polyamine than the first medium;
• b) innoculating the first and the second medium with an organism;
• and
• c) determining the growth of the organism, wherein a difference in growth of the organism between the first and second medium indicates that the test compound is a candidate for an antibiotic.