國家衛生研究院 NHRI:Item 3990099045/9498
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    题名: Comparative phosphoproteomics reveals the role of AmpC beta-lactamase phosphorylation in the clinical imipenem-resistant strain acinetobacter baumannii SK17
    其它题名: Comparative phosphoproteomics reveals the role of AmpC β-lactamase phosphorylation in the clinical imipenem-resistant strain acinetobacter baumannii SK17
    作者: Lai, JH;Yang, JT;Chern, J;Chen, TL;Wu, WL;Liao, JH;Tsai, SF;Liang, SY;Chou, CC;Wu, SH
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Nosocomial infectious outbreaks caused by multidrug-resistant Acinetobacter baumannii have emerged as a serious threat to human health. Phosphoproteomics of pathogenic bacteria has been used to identify the mechanisms of bacterial virulence and antimicrobial resistance. In this study, we used a shotgun strategy combined with high-accuracy mass spectrometry to analyze the phosphoproteomics of the imipenem-susceptible strain SK17-S and -resistant strain SK17-R. We identified 410 phosphosites on 248 unique phosphoproteins in SK17-S and 285 phosphosites on 211 unique phosphoproteins in SK17-R. The distributions of the Ser/Thr/Tyr/Asp/His phosphosites in SK17-S and SK17-R were 47.0%/27.6%/12.4%/8.0%/4.9% versus 41.4%/29.5%/17.5%/6.7%/4.9%, respectively. The Ser-90 phosphosite, located on the catalytic motif (SVSK)-V-88-K-90 of the AmpC beta-lactamase, was first identified in SK17-S. Based on site-directed mutagenesis, the nonphosphorylatable mutant S90A was found to be more resistant to imipenem, whereas the phosphorylation-simulated mutant S90D was sensitive to imipenem. Additionally, the S90A mutant protein exhibited higher beta-lactamase activity and conferred greater bacterial protection against imipenem in SK17-S compared with the wild-type. In sum, our results revealed that in A. baumannii, Ser-90 phosphorylation of AmpC negatively regulates both beta-lactamase activity and the ability to counteract the antibiotic effects of imipenem. These findings highlight the impact of phosphorylation-mediated regulation in antibiotic-resistant bacteria on future drug design and new therapies.
    日期: 2016-01
    關聯: Molecular and Cellular Proteomics. 2016 Jan;15(1):12-25.
    Link to: http://dx.doi.org/10.1074/mcp.M115.051052
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1535-9484&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000367461000002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84955466254
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