Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, United States of America.
Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, United States of America.
PLoS Negl Trop Dis. 2020 Sep 18;14(9):e0008688. doi: 10.1371/journal.pntd.0008688. eCollection 2020 Sep.
Yersinia pestis, the causative agent of plague, is a highly lethal pathogen transmitted by the bite of infected fleas. Once ingested by a flea, Y. pestis establish a replicative niche in the gut and produce a biofilm that promotes foregut colonization and transmission. The rat flea Xenopsylla cheopis is an important vector to several zoonotic bacterial pathogens including Y. pestis. Some fleas naturally clear themselves of infection; however, the physiological and immunological mechanisms by which this occurs are largely uncharacterized. To address this, RNA was extracted, sequenced, and distinct transcript profiles were assembled de novo from X. cheopis digestive tracts isolated from fleas that were either: 1) not fed for 5 days; 2) fed sterile blood; or 3) fed blood containing ~5x108 CFU/ml Y. pestis KIM6+. Analysis and comparison of the transcript profiles resulted in identification of 23 annotated (and 11 unknown or uncharacterized) digestive tract transcripts that comprise the early transcriptional response of the rat flea gut to infection with Y. pestis. The data indicate that production of antimicrobial peptides regulated by the immune-deficiency pathway (IMD) is the primary flea immune response to infection with Y. pestis. The remaining infection-responsive transcripts, not obviously associated with the immune response, were involved in at least one of 3 physiological themes: 1) alterations to chemosensation and gut peristalsis; 2) modification of digestion and metabolism; and 3) production of chitin-binding proteins (peritrophins). Despite producing several peritrophin transcripts shortly after feeding, including a subset that were infection-responsive, no thick peritrophic membrane was detectable by histochemistry or electron microscopy of rat flea guts for the first 24 hours following blood-feeding. Here we discuss the physiological implications of rat flea infection-responsive transcripts, the function of X. cheopis peritrophins, and the mechanisms by which Y. pestis may be cleared from the flea gut.
鼠疫耶尔森菌是鼠疫的病原体，通过感染跳蚤的叮咬传播，具有高度致命性。一旦被跳蚤摄入，Y. pestis 在肠道中建立一个复制生态位，并产生生物膜，促进前肠定植和传播。褐家鼠跳蚤 Xenopsylla cheopis 是几种人畜共患细菌病原体（包括 Y. pestis）的重要媒介。有些跳蚤自然清除感染；然而，这种情况发生的生理和免疫机制在很大程度上仍未得到阐明。为了解决这个问题，从未进食 5 天的跳蚤、喂食无菌血液的跳蚤或喂食含有约 5x108 CFU/ml Y. pestis KIM6+血液的跳蚤的肠道中提取 RNA，进行测序，并从头组装出不同的转录谱。对转录谱的分析和比较导致鉴定了 23 个注释的（和 11 个未知或未描述的）消化道转录本，这些转录本构成了大鼠跳蚤肠道对 Y. pestis 感染的早期转录反应。数据表明，由免疫缺陷途径（IMD）调节的抗菌肽的产生是跳蚤对 Y. pestis 感染的主要免疫反应。其余感染反应性转录本，与免疫反应没有明显关联，与至少 3 个生理主题之一有关：1）化学感觉和肠道蠕动的改变；2）消化和代谢的修饰；3）几丁质结合蛋白（围食膜蛋白）的产生。尽管在喂食后不久就产生了几种围食膜蛋白转录本，包括一组感染反应性转录本，但在首次血液喂食后 24 小时内，通过大鼠跳蚤肠道的组织化学或电子显微镜检查，未检测到厚围食膜。在这里，我们讨论了大鼠跳蚤感染反应性转录本的生理意义、X. cheopis 围食膜蛋白的功能以及 Y. pestis 可能从跳蚤肠道中清除的机制。
