Functional role of secreted chaperonins in the establishment of intracellular bacteria

对生活在细胞内的微生物的研究对于理解持续和慢性感染是如何存在的至关重要。生活在环境中的微生物是如何首先获得在我们自己的细胞中定居的能力的？正在进行的研究表明，一些环境细菌之所以获得这种能力，是因为它们经常与贪婪的变形虫和其他不断以细菌为食的原生动物接触。其中一种细菌是嗜肺军团菌，它会意外地感染吸入空调、淋浴等产生的受污染水滴的人的肺部。因此，问题仍然是，军团菌是如何从原生动物跳到人类身上的？LP通过媒体对退伍军人症爆发的报道而闻名，它是一种寄生虫，最早学会在阿米巴体内生活。因此，LP构成了一个非常有吸引力的模式生物，可以研究相对原始的分子适应阿米巴攻击，并使其一直进入更复杂的人类细胞。我的研究重点是这些原始(祖先)分子中的一种，即众所周知的Hsp60伴侣蛋白。我们知道HSP60很重要，而且非常古老，因为它存在于所有细胞生命形式中，细胞没有它就不能生存。我已经证明，LP HSP60是一种致病因子，帮助LP进入细胞，然后改变基本的细胞过程，如细胞骨架的组织和细胞器的细胞内运动。为了完成这一任务，伴侣需要从LP出来，到达阿米巴或人类细胞，所以我也在研究LP是如何分泌这种蛋白质的。在我的研究中，我将应用传统的微生物技术、光学和电子显微镜以及遗传工具。研究LP Hsp60伴侣蛋白所获得的知识可以帮助我们(I)更好地了解生活在我们细胞内的其他(也许更危险的)微生物是如何导致疾病的，(Ii)预防由这些微生物引起的疾病，以及(Iii)提供更安全的水供应，降低疾病传播的风险。

The study of microbes that live inside cells is central to understanding how persistent and chronic infections came to exist. How a microorganism that lives in the environment first acquires the ability to take residence in our own very cells? Ongoing investigations suggest that some environmental bacteria acquire this ability in response to the frequent encounters with voracious amoebas and other protozoa that are constantly feeding on bacteria. One of these bacteria is Legionella pneumophila (Lp), which accidentaly infects the lungs of humans that inhale contaminated water droplets produced in air conditioners, showers, etc. So, the question remains as to how Lp was able to leap from protozoa to humans? Lp, best known through the media coverage of Legionnaires' disease outbreaks, is a parasite that first learned to live inside amoeba. Therefore, Lp constitutes a very attractive model organism to study the adaptation of relatively primitive molecules to survive amoebal attacks, and make it all the way into the more complex human cells. My research focuses on one of these primitive (ancestral) molecules, the protein known as Hsp60 chaperonin. We know that Hsp60 is important and very old because it is present in all cellular life forms, and cells cannot live without it. I have shown that the Lp Hsp60 is a disease-causing factor that helps Lp get into cells, and then alters fundamental cellular processes like the organization of the cell's skeleton and the intracellular movement of organelles. To fulfill this mission the chaperonin needs to get outside from Lp and reach amoeba or the human cells, so I am also investigating how Lp secretes this protein. In my research, I will apply traditional microbiological techniques, light and electron microscopy, as well as genetic tools. The knowledge acquired studying the Lp Hsp60 chaperonin could help us to (i) better understand how other (perhaps more dangerous) microbes that live inside our cells cause disease, (ii) prevent the diseases caused by these microbes, and (iii) provide a safer water supply, lowering the risk of disease transmission.