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DNA Plasmid Curing to Fight Drug-Resistant Bacteria

The health risks from an increasing prevalence of drug-resistant bacteria and a diminishing antibiotic pipeline is of serious concern to the DoD, not only in regards to health care associated infections, but also threats posed from pandemics, emerging infectious pathogens and the intentional use of resistant pathogens for bioterrorism.

In the battle against these germs, the Defense Advanced Research Projects Agency (DARPA) is soliciting innovative ideas for controlling antibiotic resistant or highly virulent pathogens through plasmid curing.

One of the major routes by which bacterial pathogens become resistant to antibiotics and more virulent is through Horizontal Gene Transfer (HGT), which allows for genetic material transfer in the form of extrachromosomal plasmids from one cell to another.  This phenomenon is capable of transferring resistance or virulence genes to normally antibiotic susceptible and avirulent bacteria. This creates a severe risk to front line antibiotic treatments, such as methicillin-resistant Staphylococcus aureus (MRSA).

One way to reverse the resistance of emerging or engineered bacteria created by HGT may be to specifically target the plasmids being transferred between the cells, rather than using methods to directly kill the cells, an approach known as plasmid curing.

Proposals are sought to develop a novel plasmid curing therapeutic capable of displacing antibiotic resistance or virulence causing plasmids from bacteria.  Studies working with ESKAPE bacteria (Enterococcus, Staphylococcus, Klebsiella, Acinetobacter, Pseudomonas, and bacteria that produce Extended Spectrum Beta Lactamase) enzymes are specifically encouraged.

More information in the DARPA Small Business Innovative Research (SBIR) topic is available here.

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