Antimicrobial Drug Targeted to Essential Bacterial Genes in Wound Infection Pathogens

Wounds infected with drug-resistant Gram-negative bacteria can increase morbidity, hospital length of stay and cost. Among these Klebsiella pneumoniae and Pseudomonas aeruginosa have become important causes of concern in military personnel wounded in battlefield. New classes of antimicrobial agents are needed to combat this threat. Emerging work has focused on a new type of strategy through gene silencing by antisense mechanisms to block intracellular synthesis of housekeeping proteins via inhibition of mRNA. Among the various antisense molecules Peptide Nucleic Acids (PNAs) have several advantages and are ideally suited for development as antibacterial agents. PNAs are resistant to nucleases, proteases, and degradative enzymes, have a high binding affinity and a long half-life compared inside the cells compared to antibiotics. Therefore, in this Phase I Agave BioSystems proposes to develop antisense PNA molecules to block synthesis of housekeeping proteins in K. pneumoniae