Listeriolysin S: A bacteriocin from Listeria monocytogenes that induces membrane permeabilization in a contact-dependent manner.
Listeriolysin S: A bacteriocin from Listeria monocytogenes that induces membrane permeabilization in a contact-dependent manner.
复制标题
DOI：
10.1073/pnas.2108155118
复制
发表时间：
2021-10-05
影响因子：
11.1
通讯作者：
Pizarro-Cerdá J
中科院分区：
文献类型：
--
作者：
Meza-Torres J;Lelek M;Quereda JJ;Sachse M;Manina G;Ershov D;Tinevez JY;Radoshevich L;Maudet C;Chaze T;Giai Gianetto Q;Matondo M;Lecuit M;Martin-Verstraete I;Zimmer C;Bierne H;Dussurget O;Cossart P;Pizarro-Cerdá J
单核细胞增生李斯特菌（Lm）是一种引起李斯特菌病的细菌病原体，李斯特菌病是一种食源性疾病，以胃肠炎、脑膜炎、菌血症和孕妇流产为特征。最严重的人类李斯特菌病暴发与Lm高毒性克隆亚群有关，这些克隆编码细菌素李斯特菌溶素S (LLS)，可以改变肠道微生物群，使Lm肠道定植和侵入更深的器官。我们目前的工作确定了LLS在与肠道共生菌竞争中表现出的杀伤机制，表明它诱导目标细菌的膜渗透和膜去极化。此外，我们发现LLS是一种噻唑/恶唑修饰的微霉素，具有接触依赖的抑制机制。李斯特菌溶素S （Listeriolysin S， LLS）是一种由单核增生李斯特菌高毒力克隆产生的噻唑/恶唑修饰微霉素（TOMM）。LLS针对特定的革兰氏阳性菌，调节宿主肠道菌群组成。为了研究LLS向目标菌转移的机制及其杀菌功能，我们首先研究了LLS在LLS产生菌中的亚细胞分布。通过亚细胞分离实验、透射电子显微镜和单分子超分辨显微镜，我们发现LLS仍然与细菌细胞膜和细胞质相关，而不是分泌到细菌的细胞外空间。只有活的产生lls的细菌（而不是纯化的lls阳性细菌膜）显示出杀菌活性。应用transwell共培养系统和微流体耦合显微镜，我们确定LLS需要在LLS生产者和目标细菌之间直接接触以显示杀菌活性，因此表现为接触依赖的细菌素。接触依赖暴露于LLS导致目标细菌细胞膜的渗透/去极化和三磷酸腺苷（ATP）释放。此外，我们发现脂磷胆酸（LTAs）可以与LLS相互作用，并且LTA修饰会影响细菌对LLS的敏感性。总之，我们的研究结果表明，LLS是一种表现出接触依赖抑制机制的TOMM。
Listeria monocytogenes (Lm) is a bacterial pathogen that causes listeriosis, a foodborne disease characterized by gastroenteritis, meningitis, bacteremia, and abortions in pregnant women. The most severe human listeriosis outbreaks are associated with a subset of Lm hypervirulent clones that encode the bacteriocin Listeriolysin S (LLS), which modifies the gut microbiota and allows efficient Lm gut colonization and invasion of deeper organs. Our present work identifies the killing mechanism displayed by LLS to outcompete gut commensal bacteria, demonstrating that it induces membrane permeabilization and membrane depolarization of target bacteria. Moreover, we show that LLS is a thiazole/oxazole–modified microcin that displays a contact-dependent inhibition mechanism. Listeriolysin S (LLS) is a thiazole/oxazole–modified microcin (TOMM) produced by hypervirulent clones of Listeria monocytogenes. LLS targets specific gram-positive bacteria and modulates the host intestinal microbiota composition. To characterize the mechanism of LLS transfer to target bacteria and its bactericidal function, we first investigated its subcellular distribution in LLS-producer bacteria. Using subcellular fractionation assays, transmission electron microscopy, and single-molecule superresolution microscopy, we identified that LLS remains associated with the bacterial cell membrane and cytoplasm and is not secreted to the bacterial extracellular space. Only living LLS-producer bacteria (and not purified LLS-positive bacterial membranes) display bactericidal activity. Applying transwell coculture systems and microfluidic-coupled microscopy, we determined that LLS requires direct contact between LLS-producer and -target bacteria in order to display bactericidal activity, and thus behaves as a contact-dependent bacteriocin. Contact-dependent exposure to LLS leads to permeabilization/depolarization of the target bacterial cell membrane and adenosine triphosphate (ATP) release. Additionally, we show that lipoteichoic acids (LTAs) can interact with LLS and that LTA decorations influence bacterial susceptibility to LLS. Overall, our results suggest that LLS is a TOMM that displays a contact-dependent inhibition mechanism.
登录
查看更多内容
影响因子：
3.8
作者：
Davies, Oluwafemi;Mendes, Pedro;Malys, Naglis
通讯作者：
Malys, Naglis
影响因子：
7.7
作者：
Garcia-Bayona, Lenor;Guo, Monica S.;Laub, Michael T.
通讯作者：
Laub, Michael T.
影响因子：
3.6
作者：
Chandrangsu P;Dusi R;Hamilton CJ;Helmann JD
通讯作者：
Helmann JD
影响因子：
11.4
作者：
Gutknecht, R;Beutler, R;Erni, B
通讯作者：
Erni, B
影响因子：
4.8
作者：
Gonzalez, David J.;Lee, Shaun W.;Dorrestein, Pieter C.
通讯作者：
Dorrestein, Pieter C.