Institute for Medical Microbiology, University Medical Center Göttingen, 37075 Göttingen, Germany.
Department of Medical Microbiology, Maseno University Medical School, Private Bag, 40105 Maseno, Kenya.
Proteomics Clin Appl. 2019 May;13(3):e1800083. doi: 10.1002/prca.201800083. Epub 2018 Oct 11.
Bile acids are crucial components of the intestinal antimicrobial defense and represent a significant stress factor for enteric pathogens. Adaptation processes of Campylobacter jejuni to this hostile environment are analyzed in this study by a proteomic approach.
Proteome profiling by label-free mass spectrometry (SWATH-MS) has been used to characterize the adaptation of C. jejuni to sublethal concentrations of seven bile acids.
The bile acids with the lowest inhibitory concentration (IC ), deoxycholic and chenodeoxycholic acid, induce the most significant proteome changes. Overall a downregulation of all basic biosynthetic pathways and a general decrease in the transcription machinery are found. Concurrently, an induction of factors involved in detoxification of reactive oxygen species, protein folding, and bile acid exporting efflux pumps is detected. Exposure to deoxycholic and chenodeoxycholic acid results in an increased expression of components of the more energy-efficient aerobic respiration pathway, while the anaerobic branches of the electron transport chain are down-expressed.
The results show that C. jejuni has a differentiated system of adaptation to bile acid stresses. The findings enhance the understanding of the pathogenesis of campylobacteriosis, especially for survival of C. jejuni in the human intestine, and may provide clues to future medical treatment.
胆汁酸是肠道抗菌防御的重要组成部分,也是肠道病原体的一个重要应激因素。本研究通过蛋白质组学方法分析空肠弯曲菌对这种恶劣环境的适应过程。
采用无标记质谱(SWATH-MS)进行蛋白质组谱分析,以表征空肠弯曲菌对七种低致死浓度胆汁酸的适应情况。
具有最低抑制浓度(IC)的胆汁酸,脱氧胆酸和鹅脱氧胆酸,诱导最显著的蛋白质组变化。总体而言,所有基本生物合成途径下调,转录机制普遍下降。同时,检测到与活性氧解毒、蛋白质折叠和胆汁酸输出外排泵相关的因子诱导。暴露于脱氧胆酸和鹅脱氧胆酸会导致更节能的需氧呼吸途径的组成部分表达增加,而电子传递链的厌氧分支则表达下调。
结果表明,空肠弯曲菌有一套分化的适应胆汁酸应激的系统。这些发现增强了对弯曲菌病发病机制的理解,特别是空肠弯曲菌在人肠道中的生存能力,并且可能为未来的治疗提供线索。