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Antibiotics have been extensively used to treat S. aureus infections. However, when antibiotics are used at sub-inhibitory concentrations, especially for \u03b2-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\u2013antibiotic combinatorial treatment against S. aureus infections and provide a new perspective on the development of antibiotic adjuvants.<\/jats:p>","DOI":"10.3390\/antibiotics11060819","type":"journal-article","created":{"date-parts":[[2022,6,18]],"date-time":"2022-06-18T09:51:11Z","timestamp":1655545871000},"page":"819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antivirulence Agent as an Adjuvant of \u03b2-Lactam Antibiotics in Treating Staphylococcal Infections"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6877-6388","authenticated-orcid":false,"given":"Peng","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxin","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherlock Shing Chiu","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradeep","family":"Halebeedu Prakash","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7612-0864","authenticated-orcid":false,"given":"Ho Ting Venice","family":"Iu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hin Cheung Bill","family":"Yam","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan Hon Kwan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"Department of Microbiology, Queen Mary Hospital, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-1308","authenticated-orcid":false,"given":"Pak Leung","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"Department of Microbiology, Queen Mary Hospital, Hong Kong, China"},{"name":"State Key Laboratory of Emerging Infectious Diseases and the Research Centre of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"Carol Yu Centre for Infection, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Davies","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard Yi Tsun","family":"Kao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"},{"name":"State Key Laboratory of Emerging Infectious Diseases and the Research Centre of Infection and Immunology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ftx005","DOI":"10.1093\/femspd\/ftx005","article-title":"Staphylococcus aureus pathogenesis in diverse host environments","volume":"75","author":"Balasubramanian","year":"2017","journal-title":"Pathog. 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