Parallel exploitation of diverse host nutrients enhances Salmonella virulence.
Parallel exploitation of diverse host nutrients enhances Salmonella virulence.
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DOI：
10.1371/journal.ppat.1003301
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发表时间：
2013
期刊：
影响因子：
6.7
通讯作者：
Bumann D
中科院分区：
文献类型：
--
作者：
Steeb B;Claudi B;Burton NA;Tienz P;Schmidt A;Farhan H;Mazé A;Bumann D
病原体在受感染组织中获得宿主营养是病原体生长和毒力、疾病进展和感染控制的基础。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，竞争性感染和计算方法，以获得一个全面的概述沙门氏菌的营养和生长在小鼠伤寒模型。数据显示，沙门氏菌在受感染的组织中获得了一组出乎意料的多样化的至少31种不同的宿主营养素，但单个营养素仅以稀缺的量提供。沙门氏菌通过表达多功能分解代谢途径来适应这种情况，以同时利用多种宿主营养素。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量的独立大规模实验数据完全一致，并正确预测了738个实验突变体毒力表型的92%，这表明我们的分析提供了感染期间宿主营养供应，沙门氏菌代谢和沙门氏菌生长的全面概述。其他病原体的代谢网络的比较表明，复杂的宿主/病原体营养界面是许多感染性疾病的共同特征。传染病是世界范围内的主要健康问题。为了引起疾病，病原体需要获得宿主营养以在受感染的组织中生长并表达毒力因子。在这项研究中，我们调查了沙门氏菌的营养和生长在一个良好的特征小鼠模型的人伤寒。我们使用一组具有代谢缺陷的沙门氏菌突变体来评估沙门氏菌生长的各种营养利用途径的重要性。我们从这些实验数据中推导出一个计算模型，该模型预测营养吸收率、代谢途径的活性以及沙门氏菌酶缺陷对体内生长的影响。这些预测中的绝大多数与独立的实验数据非常一致，表明该模型提供了感染期间沙门氏菌代谢的一致概述。数据显示，沙门氏菌依赖于具有许多不同宿主营养素的高度复杂的饮食，但这些营养素中的每一种都只能以稀缺的量获得。沙门氏菌为了生长和致病，必须同时利用这些多种多样的降解途径的各种营养物质。类似的复杂病原体饮食也可能导致许多其他传染病。
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. Infectious diseases are a major health problem worldwide. To cause disease, pathogens need to acquire host nutrients for growth in infected tissues and for the expression of virulence factors. In this study, we investigated Salmonella nutrition and growth in a well-characterized mouse model of human typhoid fever. We used a panel of Salmonella mutants with metabolic defects to assess the importance of various nutrient utilization pathways for Salmonella growth. We derived from these experimental data a computational model that predicts nutrient uptake rates, activity of metabolic pathways, and the effects of Salmonella enzyme defects on in vivo growth. The vast majority of these predictions were in close agreement with independent experimental data suggesting the model provided a consistent overview of Salmonella metabolism during infection. The data showed that Salmonella depend on a highly complex diet with many different host nutrients, but each of these nutrients is available in only scarce amounts. To grow and cause disease, Salmonella must simultaneously exploit these various nutrients with versatile degradation pathways. Similar complex pathogen diets might also drive many other infectious diseases.
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影响因子：
14.9
作者：
Caspi R;Altman T;Dale JM;Dreher K;Fulcher CA;Gilham F;Kaipa P;Karthikeyan AS;Kothari A;Krummenacker M;Latendresse M;Mueller LA;Paley S;Popescu L;Pujar A;Shearer AG;Zhang P;Karp PD
通讯作者：
Karp PD
影响因子：
64.8
作者：
Arumugam, Manimozhiyan;Raes, Jeroen;Pelletier, Eric;Le Paslier, Denis;Yamada, Takuji;Mende, Daniel R.;Fernandes, Gabriel R.;Tap, Julien;Bruls, Thomas;Batto, Jean-Michel;Bertalan, Marcelo;Borruel, Natalia;Casellas, Francesc;Fernandez, Leyden;Gautier, Laurent;Hansen, Torben;Hattori, Masahira;Hayashi, Tetsuya;Kleerebezem, Michiel;Kurokawa, Ken;Leclerc, Marion;Levenez, Florence;Manichanh, Chaysavanh;Nielsen, H. Bjorn;Nielsen, Trine;Pons, Nicolas;Poulain, Julie;Qin, Junjie;Sicheritz-Ponten, Thomas;Tims, Sebastian;Torrents, David;Ugarte, Edgardo;Zoetendal, Erwin G.;Wang, Jun;Guarner, Francisco;Pedersen, Oluf;de Vos, Willem M.;Brunak, Soren;Dore, Joel;Weissenbach, Jean;Ehrlich, S. Dusko;Bork, Peer
通讯作者：
Bork, Peer
影响因子：
4.8
作者：
AbuOun, Manal;Suthers, Patrick F.;Anjum, Muna F.
通讯作者：
Anjum, Muna F.
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
2.8
作者：
Buchmeier, NA;Libby, SJ
通讯作者：
Libby, SJ