Abstract: The present invention utilizes three families of bacterial enzymes, which play a key role in mycothiol biosynthesis. The three families are bacterial cysteine:glucosaminyl inositol ligases (MshC) with catalytic ligase activity for ligation of glucosaminyl inositol and cysteine, bacterial acetyl-CoA:Cys-GlcN-Ins acetyltransferases (MshD) with catalytic activity for addition of an acetyl group to Cys-GlcN-Ins and bacterial MshA glycosyltransferase with catalytic activity for production of GlcNAc-Ins. The invention provides methods for using the mycothiol biosynthesis ligases, acetyltransferases or glycosyltransferases in drug screening assays to determine compounds that inhibit activity. The invention also provides inhibitors of the production or activity of the enzymes of mycothiol biosynthesis, and use of the inhibitors for treating microbial infection.

Abstract: The present invention provides compounds with activity as inhibitors of acyl glucosaminylinositol amidases with amidase activity against S-conjugate amides, particularly mycothiol-derived S-conjugate amides. Certain of the invention compounds are naturally occurring compounds obtained from marine sponges and other organisms. The invention further provides methods for using the compounds to inhibit virulence and reduce antibiotic resistance of mycothiol-producing bacteria.

Abstract: The present invention utilizes three families of bacterial enzymes, which play a key role in mycothiol biosynthesis. The three families are bacterial cysteine:glucosaminyl inositol ligases (MshC) with catalytic ligase activity for ligation of glucosaminyl inositol and cysteine, bacterial acetyl-CoA:Cys-GlcN-Ins acetyltransferases (MshD) with catalytic activity for addition of an acetyl group to Cys-GlcN-Ins and bacterial MshA glycosyltransferase with catalytic activity for production of GlcNAc-Ins. The invention provides methods for using the mycothiol biosynthesis ligases, acetyltransferases or glycosyltransferases in drug screening assays to determine compounds that inhibit activity. The invention provides for treatment of actinomycete infections in mammals using antibiotics that inhibit production or activity of the enzymes of mycothiol biosynthesis, in particular MshC, MshD or MshA, and thereby reduce the production of mycothiol and the virulence of the infecting bacteria.

Abstract: The present invention provides a family of bacterial acyl glucosaminylinositol amidases with amidase activity against S-conjugate amides, particularly mycothiol-derived S-conjugate amides. The invention amidases are characterized by a highly conserved 20 amino acid N-terminal region and four highly conserved histidine-containing regions and by having amidase activity, particularly amide hydrolase activity. The invention further provides methods for using the invention amidases in drug screening assays to determine compounds with antibiotic activity or compounds that inhibit activity or production of endogenous acyl glucosaminyl inositol amidase in bacteria. The invention further provides methods for detoxifying a toxic substance by contacting the toxic substance with an invention amidase, for example, by expression of the amidase under environmental conditions in a bacterium.

Abstract: The present invention provides compounds with activity as inhibitors of acyl glucosaminylinositol amidases with amidase activity against S-conjugate amides, particularly mycothiol-derived S-conjugate amides. Certain of the invention compounds are naturally occurring compounds obtained from marine sponges and other organisms. The invention further provides methods for using the compounds to inhibit virulence and reduce antibiotic resistance of mycothiol-producing bacteria.

Abstract: A method of detecting a member of the taxa actinomycetos is provided. A method also is provided for detecting mycothiol or precursor thereof. An antibody is provided which binds to mycothiol or a mycothiol precursor. A method is further provided for diagnosis of a subject having or at risk of having an actinomycetes-associated disorder. A method is also provided for identifying a sample with altered production of mycothiol or a precursor thereof. A method is provided for detecting mycothiol or precursor thereof in a bacterial colony. Kits are also disclosed which arc useful for detecting the presence of mycothiol or precursor thereof in a sample.

Abstract: The present invention provides a family of bacterial acyl glucosaminylinositol amidases with amidase activity against S-conjugate amides, particularly mycothiol-derived S-conjugate amides. The invention amidases are characterized by a highly conserved 20 amino acid N-terminal region and four highly conserved histidine-containing regions and by having amidase activity, particularly amide hydrolase activity. The invention further provides methods for using the invention amidases in drug screening assays to determine compounds with antibiotic activity or compounds that inhibit activity or production of endogenous acyl glucosaminyl inositol amidase in bacteria. The invention further provides methods for detoxifying a toxic substance by contacting the toxic substance with an invention amidase, for example, by expression of the amidase under environmental conditions in a bacterium.

Abstract: The present invention provides a family of bacterial acyl glucosaminylinositol amidases with amidase activity against S-conjugate amides, particularly mycothiol-derived S-conjugate amides. The invention amidases are characterized by a highly conserved 20 amino acid N-terminal region and four highly conserved histidine-containing regions and by having amidase activity, particularly amide hydrolase activity. The invention further provides methods for using the invention amidases in drug screening assays to determine compounds with antibiotic activity or compounds that inhibit activity or production of endogenous acyl glucosaminyl inositol amidase in bacteria. The invention further provides methods for detoxifying a toxic substance by contacting the toxic substance with an invention amidase, for example, by expression of the amidase under environmental conditions in a bacterium.