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Title: Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections

Abstract

Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. Here, the beta-lactam antibiotic oxacillin was shown to significantly attenuate the virulence of MRSA despite the pathogen being resistant to this drug. Oxacillin-mediated repression of the Agr quorum-sensing system and altered cell wall architecture, was associated with reduced cytolytic activity and increased susceptibility to host killing. These findings support the inclusion of -lactam antibiotics as an adjunctive anti-virulence therapy in the treatment of MRSA infections, with the potential to significantly improve patient outcomes in a safe, cost effective manner.

Authors:
; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
Sponsoring Org.:
USDOE
OSTI Identifier:
1339806
Report Number(s):
PNNL-SA-120576
Journal ID: ISSN 0022-1899; 48135; 453040220
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Journal of Infectious Diseases
Additional Journal Information:
Journal Volume: 215; Journal Issue: 1; Journal ID: ISSN 0022-1899
Country of Publication:
United States
Language:
English
Subject:
Environmental Molecular Sciences Laboratory

Citation Formats

Waters, Elaine M., Rudkin, Justine K., Coughlan, Simone, Clair, Geremy C., Adkins, Joshua N., Gore, Suzanna, Xia, Guoqing, Black, Nikki S., Downing, Tim, O'Neill, Eoghan, Kadioglu, Aras, and O'Gara, James P. Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections. United States: N. p., 2016. Web. doi:10.1093/infdis/jiw461.
Waters, Elaine M., Rudkin, Justine K., Coughlan, Simone, Clair, Geremy C., Adkins, Joshua N., Gore, Suzanna, Xia, Guoqing, Black, Nikki S., Downing, Tim, O'Neill, Eoghan, Kadioglu, Aras, & O'Gara, James P. Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections. United States. https://doi.org/10.1093/infdis/jiw461
Waters, Elaine M., Rudkin, Justine K., Coughlan, Simone, Clair, Geremy C., Adkins, Joshua N., Gore, Suzanna, Xia, Guoqing, Black, Nikki S., Downing, Tim, O'Neill, Eoghan, Kadioglu, Aras, and O'Gara, James P. Mon . "Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections". United States. https://doi.org/10.1093/infdis/jiw461.
@article{osti_1339806,
title = {Redeploying β-Lactam Antibiotics as a Novel Antivirulence Strategy for the Treatment of Methicillin-Resistant Staphylococcus aureus Infections},
author = {Waters, Elaine M. and Rudkin, Justine K. and Coughlan, Simone and Clair, Geremy C. and Adkins, Joshua N. and Gore, Suzanna and Xia, Guoqing and Black, Nikki S. and Downing, Tim and O'Neill, Eoghan and Kadioglu, Aras and O'Gara, James P.},
abstractNote = {Innovative approaches to the use of existing antibiotics is an important strategy in efforts to address the escalating antimicrobial resistance crisis. Here, the beta-lactam antibiotic oxacillin was shown to significantly attenuate the virulence of MRSA despite the pathogen being resistant to this drug. Oxacillin-mediated repression of the Agr quorum-sensing system and altered cell wall architecture, was associated with reduced cytolytic activity and increased susceptibility to host killing. These findings support the inclusion of -lactam antibiotics as an adjunctive anti-virulence therapy in the treatment of MRSA infections, with the potential to significantly improve patient outcomes in a safe, cost effective manner.},
doi = {10.1093/infdis/jiw461},
url = {https://www.osti.gov/biblio/1339806}, journal = {Journal of Infectious Diseases},
issn = {0022-1899},
number = 1,
volume = 215,
place = {United States},
year = {2016},
month = {11}
}