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Infection and Immunity, November 2008, p. 5392-5401, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.01376-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Máire Begley,1,2,3,{dagger} Peter A. Bron,1,{dagger} Sinead Heuston,1,2 Pat G. Casey,1,2 Nadine Englert,4 Jochen Wiesner,4 Hassan Jomaa,4 Cormac G. M. Gahan,1,2,5* and Colin Hill1,2

Alimentary Pharmabiotic Centre,1 Department of Microbiology, University College Cork,2 Teagasc Dairy Products Research Centre, Moorepark, Fermoy County Cork, Cork, Ireland,3 Institut für Klinische Chemie und Pathobiochemie, Justus-Liebig-Universität Giessen, Giessen, Germany,4 School of Pharmacy, University College Cork, Cork, Ireland5

Received 12 October 2007/ Returned for modification 20 January 2008/ Accepted 29 July 2008

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 V{gamma}9V{delta}2 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.

* Corresponding author. Mailing address: Department of Microbiology, University College Cork, Cork, Ireland. Phone: 353-214901363. Fax: 353-214903101. E-mail: c.gahan{at}ucc.ie

{triangledown} Published ahead of print on 2 September 2008.

Editor: V. J. DiRita

{dagger} M.B. and P.A.B. contributed equally to this work.

Infection and Immunity, November 2008, p. 5392-5401, Vol. 76, No. 11
0019-9567/08/$08.00+0     doi:10.1128/IAI.01376-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sleator, R. D., Watson, D., Hill, C., Gahan, C. G. M. (2009). The interaction between Listeria monocytogenes and the host gastrointestinal tract. Microbiology 155: 2463-2475 [Abstract] [Full Text]  


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