The metal homeostasis protein, Lsp, of Streptococcus pyogenes is necessary for acquisition of zinc and virulence.
The metal homeostasis protein, Lsp, of Streptococcus pyogenes is necessary for acquisition of zinc and virulence.
复制标题
化脓性链球菌的金属稳态蛋白 Lsp 对于获得锌和毒力是必需的。
DOI：
10.1128/iai.01299-08
复制
发表时间：
2009
影响因子：
3.1
通讯作者：
Caparon,MichaelG
中科院分区：
文献类型：
--
作者：
Weston,BenjaminF;Brenot,Audrey;Caparon,MichaelG
“Cluster 9” family lipoproteins function as ligand-binding subunits of ABC-type transporters in maintaining transition metal homeostasis and have been implicated in the virulence of several bacteria. While these proteins share high similarity, the specific metal that they recognize and whether their role in virulence directly involves metal homeostasis cannot be reliably predicted. We examined the cluster 9 protein Lsp ofStreptococcus pyogenesand found that specific deletion oflspproduced mutants highly attenuated in a murine model of soft tissue infection. Under standard in vitro conditions, growth of the Lsp−mutant was indistinguishable from that of the wild type, but growth was defective under zinc-limited conditions. The growth defect could be complemented by plasmids expressing wild-type Lsp but not Lsp engineered to lack its putative lipidation residue. Furthermore, Zn2+but not Mn2+rescued Lsp−growth, implicating Zn2+as the physiological ligand for Lsp. Mutation of residues in the putative Zn2+-binding pocket generated variants both hypo- and hyperresistant to zinc starvation, and both mutant classes displayed attenuated virulence. Together, these data suggest that Lsp is a ligand-binding component of an ABC-type zinc permease and that perturbation of zinc homeostasis inhibits the ability ofS. pyogenesto cause disease in a zinc-limited host milieu.
