头孢曲松耐药菌通过调整能量代谢相关蛋白产生耐药性

Modification of Energy Metabolism-related Proteins is Responsible for Ceftriaxone-resistance

随着抗生素药物的开发与利用,细菌在对抗药物过程中逐渐发展出各种不同的耐药机制.近年来高通量的蛋白质组学技术已逐渐用于细菌耐药性机理研究,但主要集中在对细菌外膜蛋白的作用进行分析.本文采用2-D native/SDS PAGE方法从蛋白质复合物角度分析接近生理条件的胞浆蛋白在头孢曲松耐药性中的作用.结果发现8个耐药性相关蛋白质,通过对蛋白质功能分析,揭示了细菌通过调整能量代谢相关蛋白产生耐药性的新机制.进一步对相关菌株的次抑菌浓度和生存率分析,提示MalP和SucC等关键蛋白质可作为设计和开发新型抗菌分子的作用靶点.

Outer membrane proteins of bacteria have been investigated systematically in response to antibiotic resistance by high-throughput proteomic techniques in recent years,but the data of the cytoplasmic proteins analyzed on a proteome scale are not available yet.In this study,2-D native/SDS-PAGE was first applied for characterization in cytoplasmic proteins responding to ceftriaxone-resistance in Escherichia coli.Eight proteins involved in modification of energy production and conversion were identified responsible for ceftriaxone-resistance.Among these proteins,down-regulated MalP and up-regulated SucC were found to play critical roles in response to resistance according to the MIC and survival ability analysis,and the two proteins may be candidate targets for development of novel antimicrobial drugs.