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Targeting fundamental pathways to disrupt Staphylococcus aureus survival: clinical implications of recent discoveries
Isaac P. Thomsen, George Y. Liu
Isaac P. Thomsen, George Y. Liu
Published March 8, 2018
Citation Information: JCI Insight. 2018;3(5):e98216. https://doi.org/10.1172/jci.insight.98216.
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Review

Targeting fundamental pathways to disrupt Staphylococcus aureus survival: clinical implications of recent discoveries

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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.

Authors

Isaac P. Thomsen, George Y. Liu

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Figure 3

Human immunodeficiency conditions that associate with susceptibility to S. aureus infections suggest chinks in the staphylococcal defense that are potentially amenable to intervention.

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Human immunodeficiency conditions that associate with susceptibility to ...
The epidemiology of hyper-IgE syndrome patients suggests that S. aureus is susceptible to Th17-mediated killing. Staphylococcal counterstrategies to avoid a Th17 response consist of O-acetylation of cell wall peptidoglycan to limit the release of pattern-associated molecular patterns and dampen development of a protective Th17 response (99). Predisposition to S. aureus infection in patients with chronic granulomatous disease hints at imperfect staphylococcal protection against ROS in normal hosts. This bacterial weakness could be further exploited by strategies that block staphylococcal antioxidant defenses, such as staphyloxanthin (109, 110), catalase, and superoxide dismutase (117, 118). Illustrated by Rachel Davidowitz.

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