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Bacterial Glue

By Cristina Luiggi Bacterial Glue Mélanie Hamon talks about bacteria that hijack the host’s cell-renewal process. Courtesy of Mélanie Hamon The intestinal epithelium is continually renewing itself. This is bad news for bacteria such as Shigella flexneri, which infects cells that line the gut and causes dysentery in humans. Pasteur Institute microbiologist Mélanie Hamon chats about a paper that describes how this stomach bug has evolved a wa

By | January 1, 2011

Bacterial Glue

Mélanie Hamon talks about bacteria that hijack the host’s cell-renewal process.
Courtesy of Mélanie Hamon

The intestinal epithelium is continually renewing itself. This is bad news for bacteria such as Shigella flexneri, which infects cells that line the gut and causes dysentery in humans. Pasteur Institute microbiologist Mélanie Hamon chats about a paper that describes how this stomach bug has evolved a way to stay put (Nature, 459:578-82, 2009).

The Scientist: Is the highly regulated shedding of old gut epithelial cells and regrowth of those cells every 24 hours an innate defense mechanism against bacteria?

Mélanie Hamon: It’s important for a healthy individual to keep that epithelium. Otherwise bacteria that normally colonize the gut might get into the circulatory system and cause problems. But during an infection you also want to shed that epithelium to get rid of the bacteria. Shigella flexneri has a huge battery of different mechanisms with which it is able to manipulate its host. During Shigella infection, it’s important for the bacteria to keep that epithelium because they are intracellular bacteria. If the target cells are shedding off, then they can’t maintain the infection.

TS: How does Shigella manage to keep that epithelium in place?

MH: Shigella is able to inject virulence factors from the bacterial cytosol directly into the host cell. OspE is one of those proteins that are injected. It targets the focal adhesions, which are what allow cells to adhere to a surface. [Kim et al.] show in this paper that OspE binds to one of the kinases that is important to form these focal adhesion points, and relocalizes it to the membrane where it is able to form the focal adhesions for cells to be able to bind the extracellular matrix and stay glued into place.

Download Flash player to listen to Hamon on bacteria infecting the host epithelium

Mélanie Hamon on bacteria infecting the host epithelium.

TS: The researchers—headed by Chihiro Sasakawa from the University of Tokyo—carried out these experiments in vitro, where there is no epithelium to speak of. What were they observing?

MH: In tissue culture, cells that are attached are sort of flat, because they have these arms that attach them to the plate. When the focal adhesion is degraded so that the cells can move or come off from the surface, these arms sort of retract and the cells round up. So there’s less contact of the cell with the surface. In the presence of OspE, they see more cells that stay flat. The paper is definitely a simplistic view of what’s going on in the gut.

TS: By infecting guinea pigs with a Shigella strain that expressed a mutant version of OspE that was unable to bind to the kinase and help cells form those focal adhesions, they protected these animals from the severe inflammation and diarrhea that would have afflicted them had they been infected with wild-type Shigella.

MH: That’s the clincher. Even if in vitro they’re looking at only one mechanism by which cells are adhering and forming an epithelium, they’re able to show, by specifically disrupting this one system in vivo, that this is absolutely essential.

TS: The authors end by suggesting that inhibiting OspE could prove an effective drug therapy for some bacterial infections. Do you agree?

MH: The balance between needing that epithelium and sloughing it off is so delicate, I don’t think we know enough yet how to manipulate that balance. If you force the cells to come off, you may cause a lot of damage. However, this opens this avenue for looking at how bacteria affect the epithelium during infection.

F1000 Associate Faculty Member Mélanie Hamon’s lab researches how Listeria monocytogenes, another bacterium that infects the intestinal epithelium, affects host transcription and chromatin structure. You can access a free copy of her evaluation here.

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