Method for Identifying Inhibitors of Staphylococcus Aureus

A method for identifying a candidate inhibitor that binds to a site of Staphylococcus aureus N-Succinyl-L,L-DAP Desuccinylase (DapE) or a homologue or active fragment thereof, comprising:

• obtaining the structure coordinates of amino acids of DapE or homologue or active fragment thereof;
• generating a three-dimensional model of DapE or homologue or active fragment thereof using the structure coordinates of the amino acids from DapA, wherein the model comprises a root mean square deviation from backbone atoms of said amino acids of not more than ±1.0 Å;
• determining a binding site of DapE or homologue thereof from the three-dimensional model;
• and
• performing a computer fitting analysis to identify the candidate inhibitor that interacts with the binding site.

A method for identifying a bacterial cell that is resistant to methicillin comprising providing a bacterial cell;

• generating a conjugate molecule, wherein the conjugate molecule comprises a compound that binds to N-Succinyl-L,L-DAP desuccinylase (DapE) linked to a detectable signaling molecule;
• contacting the bacterial cell with the conjugate molecule under conditions that allow for binding of the conjugate molecule with DapE;
• and
• detecting the presence or absence of conjugate molecule associated with the bacterial cell,
• wherein the bacterial cell is identified as methicillin-resistant when an amount of conjugate molecule associated with the bacterial cell is detected.