Israeli Researchers Reveal How Stressed Germs ‘Talk’ to Each Other Using Exosomes

Team from Bar-Ilan University hopes its discovery will contribute to the fight again malaria and other parasite-borne diseases.

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A cell secreting exosomes next to a cell under normal conditions.
A cell secreting exosomes next to a cell under normal conditions.Credit: Dror Eliaz
Ido Efrati
Ido Efrati

Exosomes are quite the scientific mystery. Our cells and the pathogens that infect us generate these vesicles, fluid-filled pouches, and nobody knows why, apart from a vague understanding that as they travel around the fluids of our bodies, they convey messages.

These microscopic bubbles are found in many, perhaps all, of our bodily fluids, including blood and urine. We know that. We also know that emitting these vesicles is a very efficient way for parasites — including the ones that cause malaria, leishmaniasis and sleeping sickness — to communicate among themselves. Tumor cells also communicate using exosomes; it helps them to evade our immune systems.

A new study by researchers from Israel's Bar-Ilan University, published in the March 2017 issue of PLOS Pathogens, sheds new light on the conundrum, having discovered that stressing the pathogens causes them to frantically emit exosomes.

So, the Israelis argue that heightened budding of exosomes is a signal of distress, a sort of message from a bacterium or parasite to its peers that something is wrong and they need to soldier on alone.

This kind of information is critical to the pathogens. It helps them to operate as a community and to develop immunity to drugs, among other things.

The conclusion was reached from the observation that when a pathogen is under stress, the pace of its exosome secretion escalates by up to a hundredfold.

The research was led by Prof. Shulamit Michaeli, dean of Bar-Ilan's Mina and Everard Goodman Faculty of Life Sciences. It focused on the genus of parasites that cause trypanosomiasis, also known as sleeping sickness, and leishmaniasis, whose unsightly skin lesions are called shoshanat yeriho (“rose of Jericho”) in Hebrew.

The research team stressed the parasites, including by exposing them to high temperatures that induced heat shock, and then compared them with their unshocked peers. Exosome secretion increased up to tenfold, Michaeli says: She and her colleagues observed it in real time, and even under an electron microscope.

Physically, an exosome consists of a fatty membrane that encloses molecules such as proteins and nucleic acids (like segments of DNA or RNA), that possess certain properties. Exosomes are budded off by most cell types in most organisms and are known to be critical to communication between cells, and between pathogens of the same species.

An exosome secreted by one pathogen may get taken up by another, which would then possess those properties. Think of it as a system update. For instance, the content of the exosome could confer genetic resistance to a medicine.

With messages of “stay away,” or the conference of resistance and so on, exosomes essentially help one-celled parasites in their natural selection, Michaeli sums up.

Moving from parasites to our own rebellious bodies, exosomes have also been shown, in other studies, to be “used” by cancer to proliferate. Various studies have claimed that cancer cells secrete exosomes that contain “operating instructions” on metastasis, while avoiding the immune system thanks to that fatty membrane skin. That in and of itself is good reason to continue to study these tiny bubbles in our blood and pee and everywhere else. If we can manage to disrupt this intercellular communication between nasties, it could be of real medical significance, Michaeli sums up.

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