Department of Pharmaceutical Sciences, University of Illinois at Chicago, Chicago, Illinois, USA.
Microbiol Spectr. 2023 Jun 15;11(3):e0331722. doi: 10.1128/spectrum.03317-22. Epub 2023 May 18.
The soil-dwelling bacterium Listeria monocytogenes survives a multitude of conditions when residing in the outside environment and as a pathogen within host cells. Key to survival within the infected mammalian host is the expression of bacterial gene products necessary for nutrient acquisition. Similar to many bacteria, L. monocytogenes uses peptide import to acquire amino acids. Peptide transport systems play an important role in nutrient uptake as well as in additional functions that include bacterial quorum sensing and signal transduction, recycling of peptidoglycan fragments, adherence to eukaryotic cells, and alterations in antibiotic susceptibility. It has been previously described that CtaP, encoded by , is a multifunctional protein associated with activities that include cysteine transport, resistance to acid, membrane integrity, and bacterial adherence to host cells. is located next to two genes predicted to encode membrane-bound permeases and , termed CtpP1 and CtpP2, respectively. Here, we show that CtpP1 and CtpP2 are required for bacterial growth in the presence of low concentrations of cysteine and for virulence in mouse infection models. Taken together, the data identify distinct nonoverlapping roles for two related permeases that are important for the growth and survival of L. monocytogenes within host cells. Bacterial peptide transport systems are important for nutrient uptake and may additionally function in a variety of other roles, including bacterial communication, signal transduction, and bacterial adherence to eukaryotic cells. Peptide transport systems often consist of a substrate-binding protein associated with a membrane-spanning permease. The environmental bacterial pathogen Listeria monocytogenes uses the substrate-binding protein CtaP not only for cysteine transport but also for resistance to acid, maintenance of membrane integrity, and bacterial adherence to host cells. In this study, we demonstrate complementary yet distinct functional roles for two membrane permeases, CtpP1 and CtpP2, that are encoded by genes linked to and that contribute to bacterial growth, invasion, and pathogenicity.
土壤栖居细菌李斯特菌在外部环境中以及作为宿主细胞内的病原体时，能够在多种条件下存活。在受感染的哺乳动物宿主中存活的关键是表达细菌基因产物，这些产物是获取营养所必需的。与许多细菌一样，李斯特菌使用肽输入来获取氨基酸。肽转运系统在营养吸收以及其他功能中起着重要作用，包括细菌群体感应和信号转导、肽聚糖片段的回收、与真核细胞的黏附以及抗生素敏感性的改变。先前已经描述了由编码的 CtaP 是一种与包括半胱氨酸运输、耐酸、膜完整性和细菌对宿主细胞的黏附在内的多种活性相关的多功能蛋白。位于两个编码膜结合渗透酶的基因旁边，分别称为 CtpP1 和 CtpP2。在这里，我们表明 CtpP1 和 CtpP2 是在低浓度半胱氨酸存在下细菌生长所必需的，并且在小鼠感染模型中是毒力所必需的。总之，这些数据确定了两种相关渗透酶的不同且不重叠的作用，这些作用对于李斯特菌在宿主细胞内的生长和存活是重要的。细菌肽转运系统对于营养吸收很重要，并且可能另外在各种其他作用中发挥作用，包括细菌通讯、信号转导和细菌对真核细胞的黏附。肽转运系统通常由与膜跨膜渗透酶相关的底物结合蛋白组成。环境细菌病原体李斯特菌不仅使用底物结合蛋白 CtaP 进行半胱氨酸运输，还用于耐酸、维持膜完整性和细菌对宿主细胞的黏附。在这项研究中，我们证明了两个膜渗透酶 CtpP1 和 CtpP2 的互补但又不同的功能作用，这两个酶由与编码的基因编码，有助于细菌的生长、入侵和致病性。
