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Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections
Staphylococcus aureus can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for β-lactam antibiotics, they may enhance staphylococcal pathogenicity and...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219823/ https://www.ncbi.nlm.nih.gov/pubmed/35740225 http://dx.doi.org/10.3390/antibiotics11060819 |
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author | Gao, Peng Wei, Yuanxin Tai, Sherlock Shing Chiu Halebeedu Prakash, Pradeep Iu, Ho Ting Venice Li, Yongli Yam, Hin Cheung Bill Chen, Jonathan Hon Kwan Ho, Pak Leung Davies, Julian Kao, Richard Yi Tsun |
author_facet | Gao, Peng Wei, Yuanxin Tai, Sherlock Shing Chiu Halebeedu Prakash, Pradeep Iu, Ho Ting Venice Li, Yongli Yam, Hin Cheung Bill Chen, Jonathan Hon Kwan Ho, Pak Leung Davies, Julian Kao, Richard Yi Tsun |
author_sort | Gao, Peng |
collection | PubMed |
description | Staphylococcus aureus can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for β-lactam antibiotics, they may enhance staphylococcal pathogenicity and exacerbate the infection. The combination of antivirulence agents and antibiotics may be a novel approach to controlling antibiotic-induced S. aureus pathogenicity. We have illustrated that under in vitro conditions, antivirulence agent M21, when administered concurrently with ampicillin, suppressed the expression and production of virulence factors induced by ampicillin. In a mouse peritonitis model, M21 reduced bacterial load irrespective of administration of ampicillin. In a bacteremia model, combinatorial treatment consisting of ampicillin or ceftazidime and M21 increased the survival rate of mice and reduced cytokine abundance, suggesting the suppression of antibiotic-induced virulence by M21. Different from traditional antibiotic adjuvants, an antivirulence agent may not synergistically inhibit bacterial growth in vitro, but effectively benefit the host in vivo. Collectively, our findings from this study demonstrated the benefits of antivirulence–antibiotic combinatorial treatment against S. aureus infections and provide a new perspective on the development of antibiotic adjuvants. |
format | Online Article Text |
id | pubmed-9219823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92198232022-06-24 Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections Gao, Peng Wei, Yuanxin Tai, Sherlock Shing Chiu Halebeedu Prakash, Pradeep Iu, Ho Ting Venice Li, Yongli Yam, Hin Cheung Bill Chen, Jonathan Hon Kwan Ho, Pak Leung Davies, Julian Kao, Richard Yi Tsun Antibiotics (Basel) Article Staphylococcus aureus can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for β-lactam antibiotics, they may enhance staphylococcal pathogenicity and exacerbate the infection. The combination of antivirulence agents and antibiotics may be a novel approach to controlling antibiotic-induced S. aureus pathogenicity. We have illustrated that under in vitro conditions, antivirulence agent M21, when administered concurrently with ampicillin, suppressed the expression and production of virulence factors induced by ampicillin. In a mouse peritonitis model, M21 reduced bacterial load irrespective of administration of ampicillin. In a bacteremia model, combinatorial treatment consisting of ampicillin or ceftazidime and M21 increased the survival rate of mice and reduced cytokine abundance, suggesting the suppression of antibiotic-induced virulence by M21. Different from traditional antibiotic adjuvants, an antivirulence agent may not synergistically inhibit bacterial growth in vitro, but effectively benefit the host in vivo. Collectively, our findings from this study demonstrated the benefits of antivirulence–antibiotic combinatorial treatment against S. aureus infections and provide a new perspective on the development of antibiotic adjuvants. MDPI 2022-06-17 /pmc/articles/PMC9219823/ /pubmed/35740225 http://dx.doi.org/10.3390/antibiotics11060819 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gao, Peng Wei, Yuanxin Tai, Sherlock Shing Chiu Halebeedu Prakash, Pradeep Iu, Ho Ting Venice Li, Yongli Yam, Hin Cheung Bill Chen, Jonathan Hon Kwan Ho, Pak Leung Davies, Julian Kao, Richard Yi Tsun Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections |
title | Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections |
title_full | Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections |
title_fullStr | Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections |
title_full_unstemmed | Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections |
title_short | Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections |
title_sort | antivirulence agent as an adjuvant of β-lactam antibiotics in treating staphylococcal infections |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219823/ https://www.ncbi.nlm.nih.gov/pubmed/35740225 http://dx.doi.org/10.3390/antibiotics11060819 |
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