Antibiotics for Recalcitrant Infection

DESCRIPTION (provided by applicant): The goal of the project is to develop a therapeutic capable of sterilizing recalcitrant chronic infections such as deep-seated abscess, osteomyelitis, endocarditis, and biofilms of indwelling devices. Many of these infections are essentially untreatable and lead to substantial morbidity and mortality. In many cases, recalcitrance of an infection is not caused by drug resistance. Rather, a slow-growing biofilm population harbors stationary phase and dormant persister cells that are highly tolerant to killing by antimicrobials. When antibiotic concentration drops, these cells can grow and repopulate the biofilm. In Gram-positive S. aureus, it appears that a stationary culture is made mostly of drug tolerant cells which arevirtually insensitive to killing by traditional antibiotics. There are many independent, redundant mechanisms of persister formation, and these specialized survivor cells do not have a realistic target which could be exploited for drug development. I