Shedding New Light On The Dreaded But Common Urinary Tract Infection

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If you're a woman, you've probably had a urinary tract infection before. I certainly have, my friends have—it's nothing to hide: over half of women will experience a UTI at some point in their lives. (Men, you're not home free; you too can get a UTI, but only 1 in 7 of you probably will.)

New research this week in the journal Cell Host & Microbe sheds new light on this common infection and why it often comes back. It turns out the common bacterial culprit, uropathogenic E. coli, has some secret weaponry.

UTI Primer

Let's first review how a UTI actually starts. Your urinary tract is made up of your kidneys, bladder, ureters (the tubes that transfer urine from your kidneys to your bladder), and urethra (the tube that empties urine from your bladder). A UTI occurs when a germ, usually bacteria, enters your urinary tract through your urethra. It can make its way to your bladder and even to your kidneys; the severity of symptoms differs depending on how far up the bacteria gets. If you've had the frequent urge to run to the bathroom followed by a burning sensation while you're urinating, you've had a UTI.

The Bacteria's Secret Weapon

This morning I spoke with the paper's lead researcher, Bijaya Dhakal of the Department of Pathology at the University of Utah. He and co-author Matthew Mulvey examined how uropathogenic E. coli (UPEC), the bacteria responsible for the majority of UTI cases, has an important virulence factor: the toxin α-hemolysin.

Think of virulence factors as different weapons in an arsenal. Each UPEC—think of her as a solider—has her own unique selection of weapons.

Dhakal explained that roughly half of UPEC have α-hemolysin, which is like owning a grenade from the arsenal. α-hemolysin was originally found to "punch holes in" and "blow up" red blood cells, according to Dhakal. But that's not all it can do; Dhakal's new research reveals how α-hemolysin is not only a grenade, but also a sniper rifle.

Your Urinary Tract As a Warzone

Let's say an army of UPEC invade your urinary tract and make their way up to your bladder. They attack the topmost layer of bladder cells (the epithelial cells), and this is when they bring out their sniper rifles, the α-hemolysin. These sniper rifles have their target on a certain class of protein that's responsible for keeping the cells stuck together (paxillin was the protein Dhakal studied). Dhakal emphasizes that the exact multi-step mechanism of how the sniper rifle (α-hemolysin) goes about shooting the target (paxillin) is still a bit gray, but an end effect can indeed be seen: once paxillin is shot, the bladder starts shedding its topmost layer of cells (this is called exfoliation).

But wait. These are the same cells where all the invading UPEC are. All the infected top layer cells "slough into urine," Dhakal says. "You're getting rid of cells harboring bacteria." Why would the whole army of UPEC commit suicide? This is when the sleeper units of the army come into play.

The top layer of bladder cells shed off and, as Dhakal says, "Now you expose the new cells to bacteria. It could be the strategy of bacteria to invade less differentiated deeper tissue." (By less differentiated, he means those deeper layer bladder cells are like blank canvases. Not until they come to the top do they differentiate and take on a very specific function—like how stem cells work.) The UPEC sleeper unit invades these deeper, less differentiated layers and remains quietly asleep. When these cells finally get cycled to the top layer of the bladder and differentiate, the UPEC sleeper unit wakes up, and the bacteria are alive and well. Lo and behold, your UTI returns.


"In the long run, the goal is to understand the mechanism of how recurrent infections are happening," Dhakal explains. His research is one step in that direction.

That's good news since recurrent UTIs are common—1 out of every 5 young women with a UTI will have another infection. The more UTIs you have, the more likely you are to get another one. (But it's not hopeless: you can do a few simple things to help prevent recurrent infections.)

UTIs are Just the Beginning

Dhakal works in Matthew Mulvey's lab, which has been studying UPEC for years now. In the the press release announcing the study's publication, co-author Mulvey commented on how their research goes beyond the common UTI:

"UTIs caused by UPEC strains that secrete HlyA [α-hemolysin] lead to more severe clinical symptoms and tissue damage," says Mulvey. "HlyA is also associated with other closely related strains of E. coli that cause pneumonia, meningitis or serious bloodstream infections. So, in addition to furthering our understanding of UTIs, this study may help to shed light on the mechanisms of other infectious diseases."

When our bodies our invaded, it's rarely a pretty picture. α-hemolysin was first understood as a grenade. Dhakal and Mulvey's work helped us understand it as a sniper rifle. Once we understand the weaponry, it's a lot easier to strategize a counterattack.

This program aired on January 19, 2012. The audio for this program is not available.



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