Sternkopf Lillebæk Eva Maria, Lambert Nielsen Stine, Scheel Thomasen Rikke, Færgeman Nils J, Kallipolitis Birgitte H
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Res Microbiol. 2017 Jul-Aug;168(6):547-557. doi: 10.1016/j.resmic.2017.03.002. Epub 2017 Mar 23.
The foodborne pathogen Listeria monocytogenes is the causative agent of the invasive disease listeriosis. Infection by L. monocytogenes involves bacterial crossing of the intestinal barrier and intracellular replication in a variety of host cells. The PrfA protein is the master regulator of virulence factors required for bacterial entry, intracellular replication and cell-to-cell spread. PrfA-dependent activation of virulence genes occurs primarily in the blood and during intracellular infection. In contrast, PrfA does not play a significant role in regulation of virulence gene expression in the intestinal environment. In the gastrointestinal phase of infection, the bacterium encounters a variety of antimicrobial agents, including medium- and long-chain free fatty acids that are commonly found in our diet and as active components of bile. Here we show that subinhibitory concentrations of specific antimicrobial free fatty acids act to downregulate transcription of PrfA-activated virulence genes. Interestingly, the inhibitory effect is also evident in cells encoding a constitutively active variant of PrfA. Collectively, our data suggest that antimicrobial medium- and long-chain free fatty acids may act as signals to prevent PrfA-mediated activation of virulence genes in environments where PrfA activation is not required, such as in food and the gastrointestinal tract.
食源性病原体单核细胞增生李斯特菌是侵袭性疾病李斯特菌病的病原体。单核细胞增生李斯特菌的感染涉及细菌穿过肠道屏障并在多种宿主细胞内复制。PrfA蛋白是细菌进入、细胞内复制和细胞间传播所需毒力因子的主要调节因子。毒力基因的PrfA依赖性激活主要发生在血液中以及细胞内感染期间。相比之下，PrfA在肠道环境中毒力基因表达的调节中不起重要作用。在感染的胃肠道阶段，细菌会遇到多种抗菌剂，包括我们饮食中常见的中链和长链游离脂肪酸以及胆汁的活性成分。在这里，我们表明特定抗菌游离脂肪酸的亚抑制浓度可下调PrfA激活的毒力基因的转录。有趣的是，这种抑制作用在编码PrfA组成型活性变体的细胞中也很明显。总体而言，我们的数据表明，抗菌中链和长链游离脂肪酸可能作为信号，在不需要PrfA激活的环境中，如在食物和胃肠道中，防止PrfA介导的毒力基因激活。
