From commensal to pathogen: translocation of Enterococcus faecalis from the midgut to the hemocoel of Manduca sexta.
From commensal to pathogen: translocation of Enterococcus faecalis from the midgut to the hemocoel of Manduca sexta.
复制标题
从共生到病原体：粪肠球菌的易位从中肠转移到曼达卡·塞克斯塔的血液。
DOI：
10.1128/mbio.00065-11
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发表时间：
2011
期刊：
影响因子：
6.4
通讯作者：
Handelsman J
中科院分区：
文献类型：
--
作者：
Mason KL;Stepien TA;Blum JE;Holt JF;Labbe NH;Rush JS;Raffa KF;Handelsman J
在动物的胃肠道中，宿主和原生细菌之间保持着动态的内稳态，但细菌从肠道迁移到其他器官可能导致疾病或死亡。粪肠球菌是胃肠道的共生菌；然而，肠球菌是越来越常见的医院感染的原因，死亡率高。我们研究了鳞翅目模型宿主Manduca sexta中粪伊蚊（E. faecalis） OG1RF与其在宿主中的位置相关的评论-病原体转换。粪芽孢杆菌在sexta幼虫的恶劣中肠环境中持续存在，不会引起明显的疾病，但将粪芽孢杆菌直接注射到幼虫的血液中会导致迅速死亡。此外，在苏云金芽孢杆菌杀虫毒素（一种针对中肠上皮的成孔毒素）存在的情况下，口服粪肠芽孢杆菌可导致死亡率升高。我们表明，由于苏云金芽胞杆菌毒素肠道完整性的损失与大肠杆菌的易位从胃肠道到血淋巴相关。在进入血淋巴后，粪肠杆菌在幼虫死亡前诱导先天免疫反应，表现为血细胞聚集。血细胞聚集的程度取决于粪肠杆菌进入的途径。我们的数据证明了sexta幼虫模型系统在调查粪芽孢杆菌引起的败血症方面的有效性，并澄清了该领域关于苏云金芽孢杆菌毒素暴露后导致幼虫死亡的事件的争议。这项研究提高了我们对粪肠球菌易位引起的脓毒症的认识，并为细菌的空间分布决定疾病结局的哺乳动物疾病提供了一个模型。我们证明了粪肠球菌是曼杜卡（Manduca sexta）肠道中的共生体和血液中的病原体，导致强大的免疫反应和快速死亡，我们将这一过程称为“共生体到病原体”的转换。虽然关于苏云金芽孢杆菌毒素诱导的杀伤仍然存在争议，但我们的实验室先前发现，在某些条件下，中肠微生物群对于苏云金芽孢杆菌毒素杀死排毒蝇是必不可少的（N. A. Broderick， K. F. Raffa, and J. Handelsman, Proc. Natl）。学会科学。美国文献103:15196 - 15199,2006；B. Raymond等人，Environ。微生物学通报，2009；p·r·约翰斯顿和n·克里克莫尔，苹果公司。环绕。微生物学杂志。75:5094-5099,2009)。我们和其他人已经证明，中肠微生物群在苏云金芽孢杆菌毒素杀灭中的作用取决于鳞翅目物种和苏云金芽孢杆菌毒素的配方（N. A. Broderick， K. F. Raffa, and J. Handelsman, Proc. Natl）。学会科学。美国文献103:15196 - 15199,2006；张志强，等，生物医学杂志，2009,7（11）。这项工作调和了许多明显矛盾的先前数据，并揭示了M. sexta-E。粪孢系统为哺乳动物败血症提供了一个模型。
A dynamic homeostasis is maintained between the host and native bacteria of the gastrointestinal tract in animals, but migration of bacteria from the gut to other organs can lead to disease or death. Enterococcus faecalis is a commensal of the gastrointestinal tract; however, Enterococcus spp. are increasingly frequent causes of nosocomial infections with a high mortality rate. We investigated the commensal-to-pathogen switch undergone by E. faecalis OG1RF in the lepidopteran model host Manduca sexta associated with its location in the host. E. faecalis persists in the harsh midgut environment of M. sexta larvae without causing apparent illness, but injection of E. faecalis directly into the larval hemocoel is followed by rapid death. Additionally, oral ingestion of E. faecalis in the presence of Bacillus thuringiensis insecticidal toxin, a pore-forming toxin that targets the midgut epithelium, induces an elevated mortality rate. We show that the loss of gut integrity due to B. thuringiensis toxin correlates with the translocation of E. faecalis from the gastrointestinal tract into the hemolymph. Upon gaining access to the hemolymph, E. faecalis induces an innate immune response, illustrated by hemocyte aggregation, in larvae prior to death. The degree of hemocyte aggregation is dependent upon the route of E. faecalis entry. Our data demonstrate the efficacy of the M. sexta larval model system in investigating E. faecalis-induced sepsis and clarifies controversies in the field regarding the events leading to larval death following B. thuringiensis toxin exposure. This study advances our knowledge of Enterococcus faecalis-induced sepsis following translocation from the gut and provides a model for mammalian diseases in which the spatial distribution of bacteria determines disease outcomes. We demonstrate that E. faecalis is a commensal in the gut of Manduca sexta and a pathogen in the hemocoel, resulting in a robust immune response and rapid death, a process we refer to as the “commensal-to-pathogen” switch. While controversy remains regarding Bacillus thuringiensis toxin-induced killing, our laboratory previously found that under some conditions, the midgut microbiota is essential for B. thuringiensis toxin killing of Lymantria dispar (N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196–15199, 2006; B. Raymond, et al., Environ. Microbiol. 11:2556–2563, 2009; P. R. Johnston, and N. Crickmore, Appl. Environ. Microbiol. 75:5094–5099, 2009). We and others have demonstrated that the role of the midgut microbiota in B. thuringiensis toxin killing is dependent upon the lepidopteran species and formulation of B. thuringiensis toxin (N. A. Broderick, K. F. Raffa, and J. Handelsman, Proc. Natl. Acad. Sci. U. S. A. 103:15196–15199, 2006; N. A. Broderick, et al., BMC Biol. 7:11, 2009). This work reconciles much of the apparently contradictory previous data and reveals that the M. sexta-E. faecalis system provides a model for mammalian sepsis.