A novel co-infection model with Toxoplasma and Chlamydia trachomatis highlights the importance of host cell manipulation for nutrient scavenging.
A novel co-infection model with Toxoplasma and Chlamydia trachomatis highlights the importance of host cell manipulation for nutrient scavenging.
复制标题
弓形虫和沙眼衣原体的新型共感染模型强调了宿主细胞操作对于营养物清除的重要性。
DOI：
10.1111/cmi.12060
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发表时间：
2013
影响因子：
3.4
通讯作者：
Coppens,Isabelle
中科院分区：
文献类型：
--
作者：
Romano,JuliaD;deBeaumont,Catherine;Carrasco,JoseA;Ehrenman,Karen;Bavoil,PatrikM;Coppens,Isabelle
弓形虫和沙眼衣原体是专性细胞内病原体，它们已进化出类似的策略在哺乳动物细胞内复制。已知这两种病原体都会广泛重塑细胞骨架，并将内吞和胞吐细胞器招募到各自的液泡中。然而，这些活动对于任一病原体的感染性有多重要仍然难以捉摸。在这里，我们开发了一种新型的联合感染系统，以深入了解弓形虫和弯曲杆菌的发育周期。 沙眼衣原体通过用两种病原体感染人体细胞，并检查它们各自复制和清除营养物质的能力。我们假设弓形虫和衣原体使用的共同策略通过两种病原体直接竞争同一营养库来实现发育结果。我们证明单个人体细胞可以携带衣原体和弓形虫。在共同感染的细胞中，弓形虫能够转移宿主细胞器的内容，例如胆固醇。因此，弓形虫的感染周期不受阻碍地进行。相反，衣原体清除选定营养物质的能力减弱，并且细菌转向应激诱导的持续生长。杀死寄生虫会导致衣原体正常发育有序恢复。我们证明C. 沙眼病患者进入应激诱导的持久表型，这是由于添加过量营养物质（例如，过量的营养物质）而无法正常营养供应的直接结果。氨基酸，导致衣原体生长和传染性的显着恢复。 C.合并感染 沙眼衣原体与弓形虫生长缓慢菌株或营养获取受损的突变体不会限制衣原体发育。相反，感染高毒力鹦鹉热衣原体的细胞中弓形虫生长停止。这项研究说明了细胞重塑在弓形虫和衣原体利用宿主细胞内资源中发挥的关键作用。它进一步强调了细胞水平上的共感染系统中细胞内病原体感染的成功与失败之间的微妙平衡。
ToxoplasmaandChlamydia trachomatisare obligate intracellular pathogens that have evolved analogous strategies to replicate within mammalian cells. Both pathogens are known to extensively remodel the cytoskeleton, and to recruit endocytic and exocytic organelles to their respective vacuoles. However, how important these activities are for infectivity by either pathogen remains elusive. Here, we have developed a novel co‐infection system to gain insights into the developmental cycles ofToxoplasmaandC. trachomatisby infecting human cells with both pathogens, and examining their respective ability to replicate and scavenge nutrients. We hypothesize that the common strategies used byToxoplasmaandChlamydiato achieve development results in direct competition of the two pathogens for the same pool of nutrients. We show that a single human cell can harbourChlamydiaandToxoplasma. In co‐infected cells,Toxoplasmais able to divert the content of host organelles, such as cholesterol. Consequently, the infectious cycle ofToxoplasmaprogresses unimpeded. In contrast,Chlamydia's ability to scavenge selected nutrients is diminished, and the bacterium shifts to a stress‐induced persistent growth. Parasite killing engenders an ordered return to normal chlamydial development. We demonstrate thatC. trachomatisenters a stress‐induced persistence phenotype as a direct result from being barred from its normal nutrient supplies as addition of excess nutrients, e.g. amino acids, leads to substantial recovery ofChlamydiagrowth and infectivity. Co‐infection ofC. trachomatiswith slow growing strains ofToxoplasmaor a mutant impaired in nutrient acquisition does not restrict chlamydial development. Conversely,Toxoplasmagrowth is halted in cells infected with the highly virulentChlamydia psittaci. This study illustrates the key role that cellular remodelling plays in the exploitation of host intracellular resources byToxoplasmaandChlamydia. It further highlights the delicate balance between success and failure of infection by intracellular pathogens in a co‐infection system at the cellular level.