Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Review

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

  • Text
  • PDF
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

×

Figure 1

S.aureus employs a variety of strategies to ensure adequate nutrition and metabolic function in resource-limited host environments.

Options: View larger image (or click on image) Download as PowerPoint

S.aureus employs a variety of strategies to ensure adequate nutrition a...
Recent insights into these pathways have revealed potential targets of intervention, as disruption of nutrient acquisition and energy production may serve to attenuate virulence. (A) A summary of metabolic adaptations of interest. S. aureus is able to utilize diverse sources of substrates to generate ATP. S. aureus produces a glutamate dehydrogenase (GudB) and an acetate kinase that can catabolize free amino acids from the host (32). Additionally, S. aureus produces a pyruvate kinase and glucose transporters that facilitate glycolysis (27–31) and is able to scavenge free lipoic acid (33). (B) Numerous critical steps have been identified for the acquisition of host metals by S. aureus. The MntABC transporter delivers manganese, which, among other roles, is a required cofactor for superoxide dismutase (17–20). α-Hemolysin–mediated (Hla-mediated) RBC lysis liberates host heme, resulting in a bacterial iron source via the Isd system (10–13). Illustrated by Rachel Davidowitz.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts