Cystathionine beta-lyase is important for virulence of Salmonella enterica serovar Typhimurium.
The biosynthesis of methionine in bacteria requires the mobilization of sulfur from Cys by the formation and degradation of cystathionine. Cystathionine beta-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 beta-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 beta-lyase is important for bacterial virulence.
Ejim
Linda J
LJ
Antimicrobial Research Centre, Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.
D'Costa
Vanessa M
VM
Elowe
Nadine H
NH
Loredo-Osti
J Concepción
JC
Malo
Danielle
D
Wright
Gerard D
GD
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D003540:Cystathionine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D008190:Lyases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011743:Pyrimidines / Q000494:pharmacology; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000401:mortality; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics / Q000472:pathogenicity*; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics; D014774:Virulence
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D003540:Cystathionine; C108337:pyrimethanil; D008715:Methionine; D008190:Lyases; C019965:cystathionine beta-lyase