Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
_version_ 1784732215542808576
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
work_keys_str_mv AT gaopeng antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT weiyuanxin antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT taisherlockshingchiu antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT halebeeduprakashpradeep antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT iuhotingvenice antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT liyongli antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT yamhincheungbill antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT chenjonathanhonkwan antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT hopakleung antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT daviesjulian antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections
AT kaorichardyitsun antivirulenceagentasanadjuvantofblactamantibioticsintreatingstaphylococcalinfections