Auxiliary genes and proteins of methicillin resistant bacteria and antagonists thereof

Abstract

The present invention is directed to the identification of mutant strains of methicillin resistant bacteria, in particular methicillin resistant Staphylococcus aureus, to identify the characteristics of such bacteria and develop drugs that can reverse, inhibit or reduce bacterial resistance to beta lactam antibiotics, e.g., methicillin. The invention particularly relates to identification of a novel mutant strain of methicillin resistant S. aureus that manifests a unique phenotype. The mutant strain lacks unsubstituted pentapeptide and incorporates alanylglutamate- and alanylisoglutamine-containing muropeptides, and accumulates large amounts of the UDP-linked muramyul dipeptide in the cytoplasmic wall precursor pool of the mutant. Based on the phenotypic consequences of the mutation, inhibitors of the lysine addition step in bacterial cell wall biosyntheis are identified as having therapeutic potential for reducing bacterial resistance to beta lactam antibiotics, notably methicillin. Accordingly, the invention provides for methods of treatment and corresponding pharmaceutical compositions for treating bacterial, particularly staphylococcal, infections.

Dependencies are inferred from the claim text.