Friday, September 6, 2019

Stomach ulcer bacterium likes bleach. Is that a way to beat it?

bottles of bleach on store shelves

A new study shows how bleach actually attracts the bacterium H. pylori, which is linked to stomach cancer.

“We found that these bacteria can swim toward sources of bleach and that it can actually tolerate pretty high concentrations and not be killed,” says Arden Perkins, a postdoctoral fellow and lead author of a new paper in PLOS Biology investigating the bacterial pathogen Helicobacter pylori and how it senses bleach at the atomic level.

“The big-picture question that this research tries to address is how these bacteria can infect someone for decades in spite of our immune system trying to eradicate it,” he says.

The answer to that question is important, researchers say, because the H. pylori bacteria infects roughly half the world’s population, is a cause of chronic inflammation and stomach ulcers, and a major risk factor for stomach cancer.

Further, the connection to bleach is important because white blood cells in the human body actually produce and secrete bleach to ward off infection.

“The same chemical compound that you would use to disinfect a countertop, at the molecular level, our immune cells are able to produce that compound,” Perkins says.

But, he says, these bacteria have figured out a way to succeed in the presence of bleach and in the human stomach, a harsh environment that most bacteria don’t inhabit. In general, bleach is still effective at killing bacteria, but for short periods of time the H. pylori bacteria can survive exposure to bleach and at much higher concentrations than expected.

To better understand how and why the bleach-sensing mechanism functioned, Perkins mapped the three-dimensional structures and chemistry of proteins to reveal the processes at work at a molecular and atomic level.

The findings show that the bacteria relied upon a particular protein known as TlpD to sense bleach. Exposure to bleach stimulates the TlpD protein to send an attractant signal to the bacteria’s flagella—threadlike tails that help bacteria move—that causes the bacteria to swim toward sources of bleach.

The research team believes that bleach may attract the H. pylori bacteria as part of a strategy to remain at sites of inflammation long term. Bleach is a hallmark of tissue inflammation, and the H. pylori bacteria make a living of promoting and inhabiting inflamed tissue for years or even decades.

The bacteria Salmonella and E. coli also have TlpD-like proteins that can detect bleach, suggesting this is a previously unrecognized strategy bacteria use to sense host inflammation, Guillemin says.

” It turns out that this is not a machinery that is exclusive to Helicobacter pylori and allows us insights into other bacteria that have similar machines.”

The research could eventually lead to new therapies to disrupt the bleach-sensing function of harmful bacteria and could have implications for reducing antibiotic resistance, the researchers say. Typical antibiotics used clinically today target things like the bacterial cell wall to kill or prevent bacteria from dividing. As a result, bacteria face selective pressure to develop resistance to those kinds of drugs in order to survive.

In the case of H. pylori, 30% of clinical isolates are now resistant to antibacterial treatment. A more thorough understanding of the mechanisms at work, Guillemin says, may help develop new, more effective means of combating bacteria.

“It might be that there are less strong selective pressures for bacteria to overcome a drug that just makes them disoriented,” Guillemin says. “By 2050 there’s going to be pandemics of antibiotic resistant bacteria so there’s a real need to think about new strategies to disrupt bacteria.”

Additional coauthors are from the University of Oregon and Stanford University. The National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Disease funded the work.

Source: University of Oregon

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