Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
J Proteome Res. 2011 Mar 4;10(3):1139-50. doi: 10.1021/pr100918u. Epub 2011 Jan 28.
Mortality attributable to infection with methicillin-resistant Staphylococcus aureus (MRSA) has now overtaken the death rate for AIDS in the United States, and advances in research are urgently needed to address this challenge. We report the results of the systematic identification of protein-protein interactions for the hospital-acquired strain MRSA-252. Using a high-throughput pull-down strategy combined with quantitative proteomics to distinguish specific from nonspecific interactors, we identified 13,219 interactions involving 608 MRSA proteins. Consecutive analyses revealed that this protein interaction network (PIN) exhibits scale-free organization with the characteristic presence of highly connected hub proteins. When clinical and experimental antimicrobial targets were queried in the network, they were generally found to occupy peripheral positions in the PIN with relatively few interacting partners. In contrast, the hub proteins identified in this MRSA PIN that are essential for network integrity and stability have largely been overlooked as drug targets. Thus, this empirical MRSA-252 PIN provides a rich source for identifying critical proteins essential for network stability, many of which can be considered as prospective antimicrobial drug targets.
耐甲氧西林金黄色葡萄球菌（MRSA）感染导致的死亡率现已超过美国的艾滋病死亡率，迫切需要研究进展来应对这一挑战。我们报告了对医院获得性 MRSA-252 菌株的蛋白质-蛋白质相互作用进行系统鉴定的结果。我们使用高通量下拉策略结合定量蛋白质组学来区分特异性和非特异性相互作用体，鉴定了涉及 608 个 MRSA 蛋白的 13219 个相互作用。连续的分析表明，这个蛋白质相互作用网络（PIN）具有无标度组织的特征，存在高度连接的枢纽蛋白。当在网络中查询临床和实验抗菌靶点时，它们通常被发现在 PIN 的外围位置，与之相互作用的伙伴相对较少。相比之下，在这个 MRSA PIN 中确定的对网络完整性和稳定性至关重要的枢纽蛋白在很大程度上被忽视了作为药物靶点。因此，这个经验性的 MRSA-252 PIN 为识别对网络稳定性至关重要的关键蛋白质提供了丰富的来源，其中许多可以被视为有前途的抗菌药物靶点。
