Methods for treatment of bacterial infections

Abstract

The peptidoglycan layer is a vital component of the bacterial cell wall, which comprises 4→3 and 3→3 transpeptide cross-linkages, the formation of which are catalyzed by D,D- and L,D-transpeptidases, respectively. Methods for the treatment of bacterial infections with agents that inhibit L,D-transpeptidases, either alone or in combination with D,D-transpeptidase inhibitors, are provided herein. Also provided are methods for the treatment of chronic stage tuberculosis with agents that inhibit enzyme with L,D-transpeptidase activity.

1 . A method for treating a subject having a bacterial infection, comprising administering to a subject in need thereof an effective amount of an agent that inhibits L, D-transpeptidase activity, thereby treating the bacterial infection. 
     
     
         2 . The method of  claim 1 , wherein the bacterial infection is caused by a Gram-negative bacterium. 
     
     
         3 . The method of  claim 1 , wherein the bacterial infection is caused by a Gram-positive bacterium. 
     
     
         4 . The method of  claim 1 , further comprising administering a βlactamase inhibitor. 
     
     
         5 . The method of  claim 1 , wherein the bacterial infection is tuberculosis. 
     
     
         6 . The method of  claim 5 , wherein tuberculosis is caused by a mycobacterial strain. 
     
     
         7 . The method of  claim 6 , wherein the strain is  Mycobacterium tuberculosis.    
     
     
         8 . The method of  claim 5 , wherein tuberculosis is chronic stage tuberculosis. 
     
     
         9 . The method of  claim 1 , wherein the L, D-transpeptidase is encoded by  Mycobacterium tuberculosis  gene ldt Mt2 . 
     
     
         10 . The method of  claim 5 , further comprising administering a β-lactamase inhibitor. 
     
     
         11 . The method of  claim 10 , wherein the β-lactamase inhibitor is clavulanic acid or a salt thereof. 
     
     
         12 . The method of  claim 1 , further comprising administering at least one antibiotic. 
     
     
         13 . The method of  claim 12 , wherein the antibiotic is a D, D-transpeptidase inhibitor. 
     
     
         14 . The method of  claim 12 , wherein the antibiotic is a β-lactam. 
     
     
         15 . The method of  claim 14 , wherein the β-lactam is amoxicillin.