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Microbiology 155 (2009), 2498-2508; DOI  10.1099/mic.0.028191-0
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Microbiology 155 (2009), 2498-2508; DOI  10.1099/mic.0.028191-0
© 2009 Society for General Microbiology

Metabolic control through ornithine and uracil of epithelial cell invasion by Shigella flexneri

Jérôme M. B. Durand and Glenn R. Björk

Department of Molecular Biology, Umeå University, S-90 187 Umeå, Sweden

This paper shows that compounds in defined growth media strongly influence the expression of the effectors of virulence in the human invasive pathogen Shigella flexneri. Ornithine in conjunction with uracil reduces the haemolytic ability of wild-type cultures more than 20-fold and the expression of the type III secretion system more than 8-fold, as monitored by an mxiC : : lacZ transcriptional reporter. mxiC gene expression is further decreased by the presence of methionine or branched-chain amino acids (15-fold or 25-fold at least, respectively). Lysine and a few other aminated metabolites (cadaverine, homoserine and diaminopimelate) counteract the ornithine-mediated inhibition of haemolytic activity and of the expression of a transcriptional activator virF reporter. The complete abolition of invasion of HeLa cells by wild-type bacteria by ornithine, uracil, methionine or branched-chain amino acids establishes that these metabolites are powerful effectors of virulence. These findings provide a direct connection between metabolism and virulence in S. flexneri. The inhibitory potential exhibited by the nutritional environment is stronger than temperature, the classical environmental effector of virulence. The implications and practical application of this finding in prophylaxis and treatment of shigellosis are discussed.

Correspondence
Glenn R. Björk
Glenn.Bjork{at}molbiol.umu.se

Abbreviations: BCAA, branched-chain amino acids; DAP, meso-diaminopimelate; T3SS, type III secretion system






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