Cinnamaldehyde targets SarA to enhance β-lactam antibiotic activity against methicillin-resistant Staphylococcus aureus  

作　　者：Jianguo Li Tingyin Lu Yuefei Chu Yuejun Zhang Jing Zhang Wenzhen Fu Jian Sun Yahong Liu Xiao-Ping Liao Yu-Feng Zhou 

机构地区：[1]State Key Laboratory for Animal Disease Control and Prevention,South China Agricultural University,Guangzhou,China [2]Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation,South China Agricultural University,Guangzhou,China [3]Yantai Fushan Center for Animal Disease Control and Prevention,Yantai,China

出　　处：《mLife》2024年第2期291-306,共16页微生物（英文）

基　　金：supported by the Guangdong Basic and Applied Basic Research Foundation(2021A1515011079);the National Natural Science Foundation of China(32172909);the National Key Research and Development Program of China(2023YFD1800100 and 2022YFD1802100);the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32121004 and 32002337);the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2019BT02N054);the Guangzhou Science and Technology Plan Project(2024A04J3412);the Double First-Class Discipline Promotion Project(2023B10564003).

摘　　要：Methicillin-resistant Staphylococcus aureus(MRSA)is a current global public health problem due to its increasing resistance to the most recent antibiotic therapies.One critical approach is to develop ways to revitalize existing antibiotics.Here,we show that the phytogenic compound cinnamaldehyde(CIN)and β-lactam antibiotic combinations can functionally synergize and resensitize clinical MRSA isolates to β-lactam therapy and inhibit MRSA biofilm formation.Mechanistic studies indicated that the CIN potentiation effect on β-lactams was primarily the result of inhibition of the mecA expression by targeting the staphylococcal accessory regulator sarA.CIN alone or in combination with β-lactams decreased sarA gene expression and increased SarA protein phosphorylation that impaired SarA binding to the mecA promoter element and downregulated virulence genes such as those encoding biofilm,α-hemolysin,and adhesin.Perturbation of SarA-mecA binding thus interfered with PBP2a biosynthesis and this decreased MRSA resistance to β-lactams.Furthermore,CIN fully restored the anti-MRSA activities of β-lactam antibiotics in vivo in murine models of bacteremia and biofilm infections.Together,our results indicated that CIN acts as a β-lactam adjuvant and can be applied as an alternative therapy to combat multidrug-resistant MRSA infections.

关 键 词：CINNAMALDEHYDE MRSA SARA β-lactamresistance 

分 类 号：Q93[生物学—微生物学] R96[医药卫生—药理学]