Antivirulence Agent as an Adjuvant of β-Lactam Antibiotics in Treating Staphylococcal Infections

• Main Authors: Peng Gao (Author), Yuanxin Wei (Author), Sherlock Shing Chiu Tai (Author), Pradeep Halebeedu Prakash (Author), Ho Ting Venice Iu (Author), Yongli Li (Author), Hin Cheung Bill Yam (Author), Jonathan Hon Kwan Chen (Author), Pak Leung Ho (Author), Julian Davies (Author), Richard Yi Tsun Kao (Author)
• Format: Book
• Published: MDPI AG, 2022-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<i>Staphylococcus aureus</i> can cause a plethora of life-threatening infections. Antibiotics have been extensively used to treat <i>S. aureus</i> 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 <i>S. aureus</i> 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 <i>S. aureus</i> infections and provide a new perspective on the development of antibiotic adjuvants.

Item Description

10.3390/antibiotics11060819
2079-6382