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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 E.; Kao, Richard Yi Tsun
Abstract
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.
Item Metadata
| Title |
Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections
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| Creator | |
| Publisher |
Multidisciplinary Digital Publishing Institute
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| Date Issued |
2022-06-17
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| 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.
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| Subject | |
| Genre | |
| Type | |
| Language |
eng
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| Date Available |
2022-09-23
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| Provider |
Vancouver : University of British Columbia Library
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| Rights |
CC BY 4.0
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| DOI |
10.14288/1.0420434
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| URI | |
| Affiliation | |
| Citation |
Antibiotics 11 (6): 819 (2022)
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| Publisher DOI |
10.3390/antibiotics11060819
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| Peer Review Status |
Reviewed
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| Scholarly Level |
Faculty; Researcher
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| Rights URI | |
| Aggregated Source Repository |
DSpace
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Item Media
Item Citations and Data
Rights
CC BY 4.0