Instituto de Investigação e Inovação em Saúde and.
Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, and.
J Infect Dis. 2017 May 1;215(9):1468-1479. doi: 10.1093/infdis/jix118.
Listeria monocytogenes is a major intracellular human foodborne bacterial pathogen. We previously revealed L. monocytogenes cadC as highly expressed during mouse infection. Here we show that L. monocytogenes CadC is a sequence-specific, DNA-binding and cadmium-dependent regulator of CadA, an efflux pump conferring cadmium resistance. CadC but not CadA is required for L. monocytogenes infection in vivo. Interestingly, CadC also directly represses lspB, a gene encoding a lipoprotein signal peptidase whose expression appears detrimental for infection. lspB overexpression promotes the release of the LpeA lipoprotein to the extracellular medium, inducing tumor necrosis factor α and interleukin 6 expression, thus impairing L. monocytogenes survival in macrophages. We propose that L. monocytogenes uses CadC to repress lspB expression during infection to avoid LpeA exposure to the host immune system, diminishing inflammatory cytokine expression and promoting intramacrophagic survival and virulence. CadC appears as the first metal efflux pump regulator repurposed during infection to fine-tune lipoprotein processing and host responses.
李斯特菌是一种主要的食源性人类细胞内细菌病原体。我们之前发现李斯特菌 cadC 在小鼠感染过程中高度表达。在这里，我们表明李斯特菌 CadC 是 CadA 的序列特异性、DNA 结合和镉依赖性调节剂，CadA 是一种赋予镉抗性的外排泵。CadC 而不是 CadA 是李斯特菌体内感染所必需的。有趣的是，CadC 还直接抑制 lspB，这是一种编码脂蛋白信号肽酶的基因，其表达似乎不利于感染。lspB 的过表达促进了 LpeA 脂蛋白向细胞外培养基的释放，诱导肿瘤坏死因子 α 和白细胞介素 6 的表达，从而损害李斯特菌在巨噬细胞中的存活。我们提出，李斯特菌在感染过程中利用 CadC 来抑制 lspB 的表达，以避免 LpeA 暴露于宿主免疫系统，减少炎症细胞因子的表达，并促进巨噬细胞内的存活和毒力。CadC 似乎是第一个在感染过程中重新用于微调脂蛋白加工和宿主反应的金属外排泵调节剂。
