Type

Journal Article

Authors

Colin Hill
Cormac G M Gahan
Hassan Jomaa
Jochen Wiesner
Nadine Englert
Pat G. Casey
Sinéad Heuston
Peter A Bron
Maire Begley

Subjects

Microbiology

Topics
genes bacterial animals molecular sequence data pathogenicity genetics mice mevalonic acid metabolism listeria monocytogenes listeriosis sequence homology nucleic acid sugar phosphates base sequence 2 c methylerythritol 4 phosphate erythritol terpenes computational biology analogs derivatives

Analysis of the isoprenoid biosynthesis pathways in Listeria monocytogenes reveals a role for the alternative 2-C-methyl-D-erythritol 4-phosphate pathway in murine infection. (2008)

Abstract Most bacteria synthesize isoprenoids through one of two essential pathways which provide the basic building block, isopentyl diphosphate (IPP): either the classical mevalonate pathway or the alternative non-mevalonate 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. However, postgenomic analyses of the Listeria monocytogenes genome revealed that this pathogen possesses the genetic capacity to produce the complete set of enzymes involved in both pathways. The nonpathogenic species Listeria innocua naturally lacks the last two genes (gcpE and lytB) of the MEP pathway, and bioinformatic analyses strongly suggest that the genes have been lost through evolution. In the present study we show that heterologous expression of gcpE and lytB in L. innocua can functionally restore the MEP pathway in this organism and confer on it the ability to induce Vgamma9 Vdelta2 T cells. We have previously confirmed that both pathways are functional in L. monocytogenes and can provide sufficient IPP for normal growth in laboratory media (M. Begley, C. G. Gahan, A. K. Kollas, M. Hintz, C. Hill, H. Jomaa, and M. Eberl, FEBS Lett. 561:99-104, 2004). Here we describe a targeted mutagenesis strategy to create a double pathway mutant in L. monocytogenes which cannot grow in the absence of exogenously provided mevalonate, confirming the requirement for at least one intact pathway for growth. In addition, murine studies revealed that mutants lacking the MEP pathway were impaired in virulence relative to the parent strain during intraperitoneal infection, while mutants lacking the classical mevalonate pathway were not impaired in virulence potential. In vivo bioluminescence imaging also confirmed in vivo expression of the gcpE gene (MEP pathway) during murine infection.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

Colin Hill, Cormac G M Gahan, Hassan Jomaa, Jochen Wiesner, Nadine Englert, Pat G. Casey, Sinéad Heuston, Peter A Bron, Maire Begley

Experts in our system

1
Colin Hill
University College Cork
Total Publications: 351
 
2
Cormac G M Gahan
University College Cork
Total Publications: 109
 
3
Pat G. Casey
University College Cork
Total Publications: 40
 
4
Maire Begley
University College Cork
Total Publications: 27