Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín, IIB-INTECH-CONICET, San Martín 1650, Buenos Aires, Argentina.
Vital Probes Inc., 1820 N. E.27th Drive, Wilton Manors, Florida, USA.
Sci Rep. 2017 Sep 6;7(1):10637. doi: 10.1038/s41598-017-11283-0.
Brucella ssp. is a facultative intracellular pathogen that causes brucellosis, a worldwide zoonosis that affects a wide range of mammals including humans. A critical step for the establishment of a successful Brucella infection is its ability to survive within macrophages. To further understand the mechanisms that Brucella utilizes to adapt to an intracellular lifestyle, a differential proteomic study was performed for the identification of intracellular modulated proteins. Our results demonstrated that at 48 hours post-infection Brucella adjusts its metabolism in order to survive intracellularly by modulating central carbon metabolism. Remarkably, low iron concentration is likely the dominant trigger for reprogramming the protein expression profile. Up-regulation of proteins dedicated to reduce the concentration of reactive oxygen species, protein chaperones that prevent misfolding of proteins, and proteases that degrade toxic protein aggregates, suggest that Brucella protects itself from damage likely due to oxidative burst. This proteomic analysis of B. abortus provides novel insights into the mechanisms utilized by Brucella to establish an intracellular persistent infection and will aid in the development of new control strategies and novel targets for antimicrobial therapy.
布鲁氏菌是一种兼性细胞内病原体，可引起布鲁氏菌病，这是一种全球性的动物传染病，影响范围广泛，包括人类。布鲁氏菌成功感染的一个关键步骤是其在巨噬细胞内存活的能力。为了进一步了解布鲁氏菌适应细胞内生活方式所利用的机制，进行了差异蛋白质组学研究，以鉴定细胞内调节蛋白。我们的研究结果表明，在感染后 48 小时，布鲁氏菌通过调节中心碳代谢来调整其代谢，以在细胞内存活。值得注意的是，低铁浓度可能是重编程蛋白质表达谱的主要触发因素。上调专门用于降低活性氧浓度的蛋白质、防止蛋白质错误折叠的伴侣蛋白以及降解有毒蛋白质聚集体的蛋白酶，表明布鲁氏菌可以保护自己免受可能由于氧化爆发而造成的损伤。对 B. abortus 的这项蛋白质组学分析为布鲁氏菌建立细胞内持续感染所利用的机制提供了新的见解，并将有助于开发新的控制策略和抗菌治疗的新靶标。
