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Robust Salmonella metabolism limits possibilities for new antimicrobials

Item Type:Article
Title:Robust Salmonella metabolism limits possibilities for new antimicrobials
Creators Name:Becker, D. and Selbach, M. and Rollenhagen, C. and Ballmaier, M. and Meyer, T.F. and Mann, M. and Bumann, D.
Abstract:New antibiotics are urgently needed to control infectious diseases. Metabolic enzymes could represent attractive targets for such antibiotics, but in vivo target validation is largely lacking. Here we have obtained in vivo information about over 700 Salmonella enterica enzymes from network analysis of mutant phenotypes, genome comparisons and Salmonella proteomes from infected mice. Over 400 of these enzymes are non-essential for Salmonella virulence, reflecting extensive metabolic redundancies and access to surprisingly diverse host nutrients. The essential enzymes identified were almost exclusively associated with a small subgroup of pathways, enabling us to perform a nearly exhaustive screen. Sixty-four enzymes identified as essential in Salmonella are conserved in other important human pathogens, but almost all belong to metabolic pathways that are inhibited by current antibiotics or that have previously been considered for antimicrobial development. Our comprehensive in vivo analysis thus suggests a shortage of new metabolic targets for broad-spectrum antibiotics, and draws attention to some previously known but unexploited targets.
Keywords:Anti-Bacterial Agents, Drug Design, Enzymes, Essential Genes, Mass Spectrometry, Proteome, Proteomics, Salmonella, Salmonella Infections, Typhoid Fever, Virulence, Animals
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group (U.K.)
Volume:440
Number:7082
Page Range:303-307
Date:16 March 2006
Official Publication:https://doi.org/10.1038/nature04616
PubMed:View item in PubMed

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