This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ejim, L. J. Articles by Wright, G. D. Search for Related Content PubMed PubMed Citation Articles by Ejim, L. J. Articles by Wright, G. D.

Cystathionine ß-Lyase Is Important for Virulence of Salmonella enterica Serovar Typhimurium

Antimicrobial Research Centre, Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada L8N 3Z5,¹ Departments of Medicine and Human Genetics, McGill University,² Center for the Study of Host Resistance, McGill University Health Center, Montréal, Québec, Canada H3G 1A4³

Received 9 November 2003/ Returned for modification 18 December 2003/ Accepted 13 February 2004

The biosynthesis of methionine in bacteria requires the mobilization of sulfur from Cys by the formation and degradation of cystathionine. Cystathionine ß-lyase, encoded by metC in bacteria and STR3 in Schizosaccharomyces pombe, catalyzes the breakdown of cystathionine to homocysteine, the penultimate step in methionine biosynthesis. This enzyme has been suggested to be the target for pyridinamine antimicrobial agents. We have demonstrated, by using purified enzymes from bacteria and yeast, that cystathionine ß-lyase is not the likely target of these agents. Nonetheless, an insertional inactivation of metC in Salmonella enterica serovar Typhimurium resulted in the attenuation of virulence in a mouse model of systemic infection. This result confirms a previous chemical validation of the Met biosynthetic pathway as a target for the development of antibacterial agents and demonstrates that cystathionine ß-lyase is important for bacterial virulence.

Editor: A. D. O'Brien

This article has been cited by other articles:

• Sperandio, B., Gautier, C., McGovern, S., Ehrlich, D. S., Renault, P., Martin-Verstraete, I., Guedon, E. (2007). Control of Methionine Synthesis and Uptake by MetR and Homocysteine in Streptococcus mutans. J. Bacteriol. 189: 7032-7044 [Abstract] [Full Text]  
• Nazi, I., Scott, A., Sham, A., Rossi, L., Williamson, P. R., Kronstad, J. W., Wright, G. D. (2007). Role of Homoserine Transacetylase as a New Target for Antifungal Agents. Antimicrob. Agents Chemother. 51: 1731-1736 [Abstract] [Full Text]  
• Sperandio, B., Polard, P., Ehrlich, D. S., Renault, P., Guedon, E. (2005). Sulfur Amino Acid Metabolism and Its Control in Lactococcus lactis IL1403. J. Bacteriol. 187: 3762-3778 [Abstract] [Full Text]