1887

Abstract

Isoprenoids may be synthesized via one of two pathways, the classical mevalonate pathway or the alternative 2--methyl--erythritol 4-phosphate (MEP) pathway. While the majority of bacteria utilize a single pathway for isoprenoid biosynthesis, is unusual in possessing the complete set of genes for both pathways. Here, we utilized new molecular tools to create precise gene deletions in selected genes encoding enzymes of both pathways, , (encoding proteins in the MEP pathway) and (encoding a protein in the mevalonate pathway). We demonstrate that the gene can only be deleted when the growth medium is supplemented with exogenous mevalonate. Furthermore, full growth of the mutant in the absence of mevalonate was only possible when the intact gene was supplied using an IPTG-inducible expression system. Murine competitive index assays performed via the oral and intraperitoneal routes of infection revealed that the mevalonate mutant could not be recovered from livers and spleens 3 days post-infection. We propose that HmgR in EGDe is involved in essential metabolic functions and that an intact MEP pathway is not capable of sustaining growth.

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2012-07-01
2019-10-20
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