中文摘要：单核细胞增生李斯特氏菌（Lm）的噬菌体元件可促进哺乳动物细胞对该菌的感染。为了寻找在Lm的生命周期中起作用的其他噬菌体残基，鉴定了一个保守位点，包含两个XRE调节子和一对编码分泌metzincin蛋白酶和结构类似于TIMP家族metzincin抑制剂的脂蛋白的基因。研究发现XRE调节因子是典型的CI/Cro调节开关，在细胞内生长条件下调节metzincin和TIMP样基因的表达。研究证实，当这些基因表达时，它们的产物改变了Lm的形态，增加了其对噬菌体介导的裂解的敏感性，从而增强了病毒粒子的释放。这些蛋白质的表达也引起细菌对细胞壁靶向化合物的敏感性，意味着它们可调节细胞壁结构。研究表明这些作用是由metzincin切割TIMP样蛋白并随后释放到细胞外环境介导的。虽然该位点对Lm致病的重要性尚不清楚，但这种噬菌体相关蛋白对作用于细菌细胞壁，有希望用于抗生素增强领域对抗耐药细菌病原体。
外文摘要：Infection of mammalian cells by Listeria monocytogenes (Lm) was shown to be facilitated by its phage elements. In a search for additional phage remnants that play a role in Lm's lifecycle, we identified a conserved locus containing two XRE regulators and a pair of genes encoding a secreted metzincin protease and a lipoprotein structurally similar to a TIMP-family metzincin inhibitor. We found that the XRE regulators act as a classic CI/Cro regulatory switch that regulates the expression of the metzincin and TIMP-like genes under intracellular growth conditions. We established that when these genes are expressed, their products alter Lm morphology and increase its sensitivity to phage mediated lysis, thereby enhancing virion release. Expression of these proteins also sensitized the bacteria to cell wall targeting compounds, implying that they modulate the cell wall structure. Our data indicate that these effects are mediated by the cleavage of the TIMP-like protein by the metzincin, and its subsequent release to the extracellular milieu. While the importance of this locus to Lm pathogenicity remains unclear, the observation that this phage-associated protein pair act upon the bacterial cell wall may hold promise in the field of antibiotic potentiation to combat antibiotic resistant bacterial pathogens.
外文关键词：Listeria monocytogenes；phage；metzincin；TIMP
作者：Boichis, E；Sigal, N；Borovok, I；Herskovits, AA
作者单位：Tel Aviv Univ
期刊名称：MICROORGANISMS
期刊影响因子：4.152
出版年份：2021
出版刊次：6
点击下载：噬菌体源mezincin和TIMP样蛋白对可引发单核增生李斯特菌对噬菌体细胞裂解酶和其他细胞壁靶向剂的敏感性