title: Parallel exploitation of diverse host nutrients enhances Salmonella virulence.
abstract: 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.
authors: Focal Area Infection Biology, Biozentrum, University of Basel, Basel, Switzerland.
authors: Benjamin
authors: B
authors: Steeb
authors: Beatrice
authors: B
authors: Claudi
authors: Neil A
authors: NA
authors: Burton
authors: Petra
authors: P
authors: Tienz
authors: Alexander
authors: A
authors: Schmidt
authors: Hesso
authors: H
authors: Farhan
authors: Alain
authors: A
authors: Mazé
authors: Dirk
authors: D
authors: Bumann
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions; D053858:Metabolic Networks and Pathways; D051379:Mice; D008807:Mice, Inbred BALB C; D040901:Proteomics; D019779:Salmonella enterica / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014435:Typhoid Fever / Q000378:metabolism / Q000382:microbiology*
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