Wolbachia Boost Stem Cell Production

The widespread bacteria known to manipulate host reproductive output can do so by ramping up stem cell division and consequent egg production in Drosophila.

Oct 20, 2011
Jef Akst

Image of several progressively more differentiated egg chambers (oldest at bottom) in Drosophila mauritiana. Wolbachia (stained in green) are highly concentrated in the GSCN, at the tip of the germarium. COURTESY OF EVA M. FAST AND HORACIO M. FRYDMAN

Wolbachia can infiltrate germline stem cells of the fruit fly Drosophila mauritiana, where it spurs increased cell division of gamete precursors and lower rates of cell death, according to a study published today (October 20) in Science Express. This incursion can result in the production of up to 4 times as many host oocytes, which the bacteria use as a vehicle for transmission to new hosts.

“I think it’s extremely interesting,” said evolutionary geneticist Jack Werren of the University of Rochester, who was not involved in the study. “It’s a significant advance on our understanding of how Wolbachia interact with their hosts…. My guess is that when researchers start to look in more detail in other systems, they’re going to find that Wolbachia are routinely manipulating stem cell biology.”

Wolbachia are widespread bacteria that infect a variety of invertebrate species. They are primarily transmitted through oocytes from mom to offspring and are notorious for their ability to manipulate the reproductive properties of their host to enhance their own proliferation. Different strains of Wolbachia can cause infected males to produce sperm that kills uninfected eggs, induce parthenogenesis in infected females—eliminating the need for reproductive mating—and can even turn males into functional females that can pass the bacteria on to their offspring.

In the new study, cell biologist Horacio Frydman of Boston University and his colleagues showed Wolbachia can increase the number of eggs produced by D. mauritiana females. Wolbachia-infected flies laid 3.5 to 4 times more eggs than uninfected individuals.

Drosophila mauritiana female laying eggs
Drosophila mauritiana female laying eggs

To understand how Wolbachia induce this increase in egg production, Frydman’s team examined the distribution of the bacteria inside flies infected with a Wolbachia strain called wMau. Electron microscopy and confocal imaging techniques demonstrated a substantial accumulation of Wolbachia in the germline stem cell niche (GSCN), where the stem cells that form the females’ eggs are stored.

“It’s quite remarkable,” Frydman said. “Most of the cytoplasm of [these stem cells] is completely filled with the bacteria.”

A closer look at the activity of the cells within the niche revealed that the stem cells of Wolbachia-infected flies were dividing at a faster rate than their uninfected counterparts—about twice as quickly. “We were quite surprised,” Frydman said. “This is the first time that it is shown that a bacterial infection can basically manipulate the rate of division of a stem cell.”

But twice the amount of cell division in the GSCN couldn’t explain the quadrupled egg production, Frydman noted—there had to be something else going on. Following the stem cells that divided and differentiated into egg cell precursors, the researchers found the answer: Compared with uninfected flies, the cells of Wolbachia-infested flies underwent only about half the amount of programmed cell death, a normal regulatory process of egg development.

Wolbachia are manipulating not only the levels of germline stem cell division, but they are blocking the rate of programmed cell death,” Frydman said. “So an infected fly is going to produce more infected eggs, and that favors the spreading of these bacteria in nature.”

Image of a succession of progressively more differentiated egg chambers in Drosophila mauritiana, originating from the germarium (top). The germline (shown in red) arises from the germline stem cells (2-3 leftmost red cells at the top).
Image of a succession of progressively more differentiated egg chambers in Drosophila mauritiana, originating from the germarium (top). The germline (shown in red) arises from the germline stem cells (2-3 leftmost red cells at the top).

The findings could have implications for the use of Wolbachia to control vector-borne diseases, an effort that has shown recent promise to limit the transmission of malaria and dengue transmission via mosquitoes, for example. (See The Scientist’s 2009 feature on the topic, Evolution, Resisted.) “This might point to a positive fitness effects of the Wolbachia, which could help Wolbachia spread in populations,” evolutionary geneticist Ary Hoffmann of The University of Melbourne, who was not involved in the research, wrote in an email to The Scientist.

A more near-term application of the discovery could be in basic stem cell research. For example, if researchers can identify the molecular pathways that the bacteria manipulate to change the rate of stem cell division—something Frydman’s lab is currently working on—“we can probably learn very fundamental things about stem cell biology,” he said. The bacteria themselves may even serve as a marker for the stem cell niches, which “are not really well characterized,” he added. Because Wolbachia seem to accumulate in these areas, “the bacteria might point us to where these other stem cell niches reside.”

“It’s rather intriguing that this microorganism has the ability to manipulate stem cell biology,” Werren agreed. “So far, [this is just] in an insect, of course, not in humans, but nevertheless there’s enough similarities in the biology of stem cells across organisms that Wolbachia could potentially be used as a tool to investigate [human] stem cell biology.”

E.M. Fast et al., “Wolbachia enhance Drosophila stem cell proliferation and target the germline stem cell niche,” Science Express, doi:10.1126/science.1209609, 2011.