The Development of Novel Antimicrobials Against Staphylococcus aureus: Current Strategies and Future Directions

Abstract

The spread of antimicrobial resistance in a wide variety of pathogens and the failure of the pharmaceutical industry to match pace with new therapeutics has resulted in a crisis situation facing the future of public health with regards to the treatment of infectious disease. Among the most notorious and dangerous of the pathogens expressing resistance to a spectrum of antibiotics is Staphylococcus aureus, a commensal of humans and a known cause of debilitating and life-threatening infections, such as necrotizing fasciitis, endocarditis, and osteomyelitis. The recent increase in aggressive tissue- destructive infections caused by community-associated methicillin-resistant S. aureus has been one of many alarming progressions that call for the development of novel therapeutic compounds and the investigation of new types of drug targets. This work summarizes the resistance crisis as it pertains to S. aureus, surveys the current understanding of the biology of this important pathogen, and explores new tactics for resolving the body’s infection with this microbe. In particular, recent work has suggested the therapeutic potential of compounds limiting the virulence of pathogens, and these techniques are reviewed in their application to S. aureus disease. In order to inform future investigation in the field, a set of suggestions are provided that seek to set a research agenda for the successful discovery of new antimicrobials.