Robust Salmonella metabolism limits possibilities for new antimicrobials

Daniel Becker, Matthias Selbach, Claudia Rollenhagen, Matthias Ballmaier, Thomas F. Meyer, Matthias Mann and Dirk Bumann ()
Additional contact information
Daniel Becker: Department of Molecular Biology
Matthias Selbach: Department of Proteomics and Signal Transduction
Claudia Rollenhagen: Department of Molecular Biology
Matthias Ballmaier: Flow Cytometry Core Facility
Thomas F. Meyer: Department of Molecular Biology
Matthias Mann: Department of Proteomics and Signal Transduction
Dirk Bumann: Department of Molecular Biology

Nature, 2006, vol. 440, issue 7082, 303-307

Abstract: 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.

Date: 2006
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/nature04616 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:440:y:2006:i:7082:d:10.1038_nature04616

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature04616

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().