Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland.
PLoS Pathog. 2013;9(4):e1003301. doi: 10.1371/journal.ppat.1003301. Epub 2013 Apr 25.
Pathogen access to host nutrients in infected tissues is fundamental for pathogen growth and virulence, disease progression, and infection control. However, our understanding of this crucial process is still rather limited because of experimental and conceptual challenges. Here, we used proteomics, microbial genetics, competitive infections, and computational approaches to obtain a comprehensive overview of Salmonella nutrition and growth in a mouse typhoid fever model. The data revealed that Salmonella accessed an unexpectedly diverse set of at least 31 different host nutrients in infected tissues but the individual nutrients were available in only scarce amounts. Salmonella adapted to this situation by expressing versatile catabolic pathways to simultaneously exploit multiple host nutrients. A genome-scale computational model of Salmonella in vivo metabolism based on these data was fully consistent with independent large-scale experimental data on Salmonella enzyme quantities, and correctly predicted 92% of 738 reported experimental mutant virulence phenotypes, suggesting that our analysis provided a comprehensive overview of host nutrient supply, Salmonella metabolism, and Salmonella growth during infection. Comparison of metabolic networks of other pathogens suggested that complex host/pathogen nutritional interfaces are a common feature underlying many infectious diseases.
病原体进入感染组织中的宿主营养物质对于病原体生长和毒力、疾病进展和感染控制至关重要。然而，由于实验和概念上的挑战，我们对这一关键过程的理解仍然相当有限。在这里，我们使用蛋白质组学、微生物遗传学、竞争感染和计算方法，在小鼠伤寒热模型中全面概述了沙门氏菌的营养和生长情况。数据显示，沙门氏菌在感染组织中能够获取一组令人惊讶的多样化的至少 31 种不同的宿主营养物质，但每种营养物质的含量都非常有限。沙门氏菌通过表达多功能的分解代谢途径来适应这种情况，从而同时利用多种宿主营养物质。基于这些数据的沙门氏菌体内代谢的基因组规模计算模型与沙门氏菌酶数量的独立大规模实验数据完全一致，并正确预测了 738 个报告的实验性突变体毒力表型中的 92%，这表明我们的分析为宿主营养供应、沙门氏菌代谢和感染期间的沙门氏菌生长提供了全面的概述。对其他病原体代谢网络的比较表明，复杂的宿主/病原体营养界面是许多传染病的共同特征。
