Cystathionine p-lyase is important for virulence of Salmonella enterica serovar typhimurium
Cystathionine p-lyase is important for virulence of Salmonella enterica serovar typhimurium
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DOI：
10.1128/iai.72.6.3310-3314.2004
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发表时间：
2004-06-01
影响因子：
3.1
通讯作者：
Wright, GD
中科院分区：
文献类型：
--
作者：
Ejim, LJ;D'Costa, VM;Wright, GD
细菌中甲硫氨酸的生物合成需要通过形成和降解胱硫醚从Cys中动员硫。由细菌中的metC和粟酒裂殖酵母中的STR 3编码的胱硫醚β-裂解酶催化胱硫醚分解为同型半胱氨酸，这是甲硫氨酸生物合成中的倒数第二步。这种酶被认为是吡啶胺类抗菌剂的靶标。我们已经证明，通过使用纯化的酶从细菌和酵母，胱硫醚β-裂解酶是不可能的目标，这些代理商。尽管如此，在鼠伤寒沙门氏菌血清型中metC的插入失活导致了全身感染小鼠模型中毒力的减弱。该结果证实了Met生物合成途径作为开发抗菌剂的靶标的先前化学验证，并证明了胱硫醚β-裂解酶对细菌毒力很重要。
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.