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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 2

Efficient evasion of both innate and adaptive host defense is paramount to the ability of S. aureus to invade and persist in humans.

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Efficient evasion of both innate and adaptive host defense is paramount ...
Staphylococcal immune evasion is mediated by several distinct pathways that appear to have high relevance in the setting of human disease and, therefore, represent potential therapeutic or preventive targets. The neutrophil is the primary mediator of innate antistaphylococcal host defense (47), and S. aureus expresses numerous proteins capable of interfering with neutrophil function, such as disruption of chemotaxis (CHIPS, refs. 79, 80) or potent lysis (the leukocidins, refs. 59–68) and phenol-soluble modulins (89–94). Human antibodies are capable of neutralizing leukocidin-mediated lysis and represent a potential target for intervention (74–76). Adaptive immunity is disrupted by the pathogen via numerous virulence factors, including staphylokinase (46) and staphylococcal protein A (SpA), which has several known functions, including avid binding of IgG Fc as well as manipulation of B cell responses (34–39). Illustrated by Rachel Davidowitz.

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