Abstract
The emergence of community-associated methicillin-resistant Staphylococcus aureus during the past decade along with an impending shortage of effective antistaphylococcal antibiotics have fueled impressive advances in our understanding of how S. aureus overcomes the host environment to establish infection. Backed by recent technologic advances, studies have uncovered elaborate metabolic, nutritional, and virulence strategies deployed by S. aureus to survive the restrictive and hostile environment imposed by the host, leading to a plethora of promising antimicrobial approaches that have potential to remedy the antibiotic resistance crisis. In this Review, we highlight some of the critical and recently elucidated bacterial strategies that are potentially amenable to intervention, discuss their relevance to human diseases, and address the translational challenges posed by current animal models.
Highlights
The progressive increase in the prevalence of antibiotic resistance within circulating strains of Staphylococcus aureus is well documented [1]
This ability to thrive in the presence of radical NO is critical for pathogenesis and depends on high level L-lactate dehydrogenase activity as well as specific glycolysis substrates
While S. aureus defenses have been well reviewed in recent years, this Review will focus on recent discoveries with high clinical relevance and logical targets for intervention against the pathogen (Figure 2)
Summary
The progressive increase in the prevalence of antibiotic resistance within circulating strains of Staphylococcus aureus is well documented [1]. The frequency of resistance to drugs, such as clindamycin, considered to be the mainstays of antistaphylococcal therapy has increased rapidly in recent years [2], and resistance to oritavancin, the most recently US-approved drug to combat methicillin-resistant S. aureus (MRSA), has already been reported [3]. A substantial number of important discoveries in the last decade have provided new insights into fundamental mechanisms, such as nutrient acquisition, key metabolic pathways, and evasion of host defenses, that allow S. aureus survival in the host. In this Review, we highlight some of these notable discoveries and discuss their clinical relevance and potential implications for developing novel interventions against this important pathogen
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