Lethal mutations in the isoprenoid pathway of Salmonella enterica

Rita M. Cornish, John R. Roth, C. Dale Poulter

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Essential isoprenoid compounds are synthesized using the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway in many gram-negative bacteria, some gram-positive bacteria, some apicomplexan parasites, and plant chloroplasts. The alternative mevalonate pathway is found in archaea and eukaryotes, including cytosolic biosynthesis in plants. The existence of orthogonal essential pathways in eukaryotes and bacteria makes the MEP pathway an attractive target for the development of antimicrobial agents. A system is described for identifying mutations in the MEP pathway of Salmonella enterica serovar Typhimurium. Using this system, point mutations induced by diethyl sulfate were found in the all genes of the essential MEP pathway and also in genes involved in uptake of methylerythritol. Curiously, none of the MEP pathway genes could be identified in the same parent strain by transposon mutagenesis, despite extensive searches. The results complement the biochemical and bioinformatic approaches to the elucidation of the genes involved in the MEP pathway and also identify key residues for activity in the enzymes of the pathway.

Original languageEnglish (US)
Pages (from-to)1444-1450
Number of pages7
JournalJournal of Bacteriology
Volume188
Issue number4
DOIs
StatePublished - Feb 2006

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Immunology

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