β-Lactam Antibiotics Enhance the Pathogenicity of Methicillin-Resistant Staphylococcus aureus via SarA-Controlled Lipoprotein-Like Cluster Expression

作者：Weilong Shang, Yifan Rao, Ying Zheng, Yi Yang, Qiwen Hu, Zhen Hu, Jizhen Yuan, Huagang Peng, Kun Xiong, Li Tan, Shu Li, Junmin Zhu, Ming Li, Xiaomei Hu, Xuhu Mao, Xiancai Rao · 发表于：mBio · 年份：2019 · DOI：10.1128/mbio.00880-19 · 被引用次数：64 · 研究领域：Antimicrobial Resistance in Staphylococcus、Streptococcal Infections and Treatments、Infective Endocarditis Diagnosis and Management

β-Lactam antibiotics are widely applied to treat infectious diseases. However, certain poor disease outcomes caused by β-lactams remain poorly understood. In this study, we have identified a cluster of lipoprotein-like genes ( lpl , sa2275 – sa2273 ) that is upregulated in the major clinically prevalent MRSA clones in response to subinhibitory concentrations of β-lactam induction. The major highlight of this work is that β-lactams stimulate the expression of SarA, which directly binds to the lpl cluster promoter region and upregulates lpl expression in MRSA. Deletion of lpl significantly decreases proinflammatory cytokine levels in vitro and in vivo . The β-lactam-induced Lpls enhance host inflammatory responses by triggering the Toll-like-receptor-2-mediated expressions of interleukin-6 and tumor necrosis factor alpha. The β-lactam-induced Lpls are important virulence factors that enhance MRSA pathogenicity. These data elucidate that subinhibitory concentrations of β-lactams can exacerbate the outcomes of MRSA infection through induction of lpl controlled by the global regulator SarA.