利用蛋白质组学研究新德里金属b-内酰胺酶1对鲍曼不动杆菌的影响

Comparative proteomics reveals the role of NDM-1 in Acinetobacter baumannii

摘要:

[目的]比较临床分离的亲缘关系近的多药耐药鲍曼不动杆菌MDR-ZJ06（bla_NDM-1^-）和ABC3229（bla_NDM-1⁺）的差异蛋白质组，以期发现新德里金属b-内酰胺酶1（New Delhimetallo-β-lactamase-1，NDM-1）对鲍曼不动杆菌生长代谢的影响。[方法]利用2-DE联合MALDI-TOF MS/MS技术鉴定差异表达蛋白，并在GO注析的基础上，对差异蛋白进行通路分析、功能分类和富集分析，并作出蛋白与蛋白相互作用网络。[结果]发现ABC3299相对于MDR-ZJ06有51个差异表达蛋白，其中11个蛋白表达上调，40个蛋白表达下调，并且这些差异蛋白主要涉及降低碳代谢、氨基酸代谢、脂肪酸代谢和细胞壁合成，增加铁离子转运系统形成。[结论]这个结果揭示了NDM-1可能是通过减缓细菌自身的代谢，增加自身铁的摄取使细菌机体系统地抵抗抗生素从而达到耐药。

Abstract:

[Objective] In order to investigate how NDM-1 affect the metabolism of A. baumannii, we analyzed the differentially expressed proteins (DEPs) between clinically isolated multidrug-resistant A. baumannii MDR-ZJ06 (bla_NDM-1^-) and ABC3229 (bla_NDM-1⁺) which have a close genetic relationship. [Methods] We used 2-DE coupled with MALDI-TOF MS/MS to analyze the differentially expressed proteins (DEPs) between A. baumannii MDR-ZJ06 and ABC3229. Based on GO annotations, we analyze DEPs by KEGG, Function classification, enrichment analysis and protein-protein interaction network. [Results] We found that there were 51 DEPs, including 11 up-regulated proteins and 41 down-regulated proteins in ABC3229. These proteins were predominantly involved in reducing carbohydrate metabolism, amino acid metabolism, fatty acid metabolism, cell wall synthesis, and increasing of iron transport system formed. [Conclusion] These results uncover the effect of NDM-1 on bacteria may be resistant to antibiotics by slowing down the metabolism of bacteria and increasing the uptake of iron, thereby the bacteria will systemic resistance antibiotics.