Infection and Immunity, June 2004, p. 3310-3314, Vol. 72, No. 6
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.6.3310-3314.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Cystathionine ß-Lyase Is Important for Virulence of Salmonella enterica Serovar Typhimurium
Linda J. Ejim,1 Vanessa M. D'Costa,1 Nadine H. Elowe,1 J. Concepción Loredo-Osti,2 Danielle Malo,2,3 and Gerard D. Wright1*
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.
* Corresponding author. Mailing address: Antimicrobial Research Centre, Department of Biochemistry, McMaster University, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5. Phone: (905) 525-9140 (ext. 22454). Fax: (905) 522-9033. E-mail: wrightge{at}mcmaster.ca.
Editor: A. D. O'Brien
Infection and Immunity, June 2004, p. 3310-3314, Vol. 72, No. 6
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.6.3310-3314.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
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Copyright © 2004 by the American Society for Microbiology. All rights reserved.