Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, 110029, India.
J Proteome Res. 2010 Feb 5;9(2):1121-8. doi: 10.1021/pr9011188.
In the recent past, Acinetobacter baumannii in hospitals has become increasingly resistant to a number of antibiotics including the latest carbapenems and this is of great concern. Here, for the first time, we report 2D-Differential In-Gel Electrophoresis (DIGE) analysis of outer membrane proteome of ATCC 19606 and carbapenem-resistant strain of A. baumannii. Using biological variance analysis (BVA), we identified 25 differentially expressed proteins with a fold difference >or=2; confidence >90% and statistical significance p <or= 0.05. By applying MALDI TOF/TOF and ESI MS/MS proteomic approach to carbapenem-resistant A. baumannii, we identified four porins whose expression was significantly downregulated and a large number of upregulated proteins with specific transport and enzymatic properties. All the following synergistically give advantage to the resistant A. baumannii for survival: (i) high expression of altered CarO isoforms with possible low influx efficiency, (ii) elevated levels of CsuA/B with high adhesive properties, (iii) overexpression of pivotal nutrient transporters, (iv) continued expression of the major OmpAb, and (v) induced production of proteins of hypothetical origin. This proteomic study provides a platform to understand the complex nature of beta-lactam resistance in A. baumannii.
在最近的一段时间里,医院中的鲍曼不动杆菌对包括最新碳青霉烯类抗生素在内的多种抗生素的耐药性不断增强,这令人非常担忧。在这里,我们首次报道了采用二维差异凝胶电泳(2D-DIGE)分析 ATCC 19606 和耐碳青霉烯类鲍曼不动杆菌的外膜蛋白组。通过生物方差分析(BVA),我们鉴定出 25 个差异表达蛋白,其 fold change 值≥2;置信度>90%,统计显著性 p <or= 0.05。通过对耐碳青霉烯类鲍曼不动杆菌应用 MALDI-TOF/TOF 和 ESI-MS/MS 蛋白质组学方法,我们鉴定出 4 种孔蛋白,其表达明显下调,以及大量具有特定转运和酶特性的上调蛋白。所有这些协同作用都使耐药性鲍曼不动杆菌具有生存优势:(i)可能低流入效率的改变型 CarO 同工型的高表达,(ii)具有高粘附特性的 CsuA/B 的高水平,(iii)关键营养转运蛋白的过度表达,(iv)主要 OmpAb 的持续表达,以及(v)假定来源蛋白的诱导产生。这项蛋白质组学研究为理解鲍曼不动杆菌中β-内酰胺类抗生素耐药性的复杂性质提供了一个平台。