Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, United States of America.
PLoS One. 2011 Mar 10;6(3):e17717. doi: 10.1371/journal.pone.0017717.
Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid.
METHODOLOGY/PRINCIPAL FINDINGS: We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death.
CONCLUSIONS/SIGNIFICANCE: Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells.
凋亡是多细胞生物清除不需要的细胞以维持组织内稳态和功能的主要方式。它的特征是垂死细胞的形态发生明显变化，这是由一系列离散的生化事件协调的。尽管在原核生物中也有原始形式的程序性细胞死亡的证据，但没有信息表明原核生物的死亡与真核细胞高度调控的程序性死亡具有机制相似性。在这项研究中，我们比较了 HAMLET（一种人乳中乳白蛋白和油酸的复合物）诱导的肿瘤细胞和细菌细胞死亡的特征。
方法/主要发现：我们表明， HAMLET 处理的细菌会发生细胞死亡，其机制和形态与肿瘤细胞的凋亡死亡相似。在 Jurkat 细胞和肺炎链球菌中，死亡伴随着类似凋亡的形态，如细胞收缩、DNA 浓缩和 DNA 降解成大小相似的高分子量片段，这是通过场反转凝胶电泳检测到的。 HAMLET 被内化到肿瘤细胞中，并与线粒体结合，导致线粒体膜迅速去极化，并与肺炎链球菌膜结合并诱导其去极化，其动力学和幅度与在线粒体中相似。这两个系统的膜去极化都需要钙转运，并且发现肿瘤细胞和细菌都需要丝氨酸蛋白酶活性（但不需要半胱天冬酶活性）来执行细胞死亡。
结论/意义：我们的结果表明，许多与凋亡相关的形态变化和生化反应都存在于原核生物中。鉴定细菌细胞死亡的机制有可能揭示新的抗菌治疗靶点，并进一步了解真核细胞细胞死亡的核心激活机制。
