Immune system's front-line defense freezes bacteria in their tracks

phys.org | 1/11/2019 | Staff
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In the moments leading up to assault by a short, peculiar peptide, the bacteria are happily growing, their DNA jiggling around the cell in the semi-random motions characteristic of life.

Seconds later, the jiggling stops. Life grinds to a halt.

Peptides—short - Chunks - Amino - Acids - Units

Some 100 million peptides—short chunks of amino acids, the basic units of proteins—by the name of LL-37 have invaded the cell, where, with strong electric charges, they've bound tightly to the machinery driving the cell, immobilizing and killing it.

"The DNA seems to freeze within seconds," says James Weisshaar, a professor of chemistry at the University of Wisconsin–Madison. "That's the weird event that got us going."

New - Work - Weisshaar - Lab - Mechanism

New work from Weisshaar's lab suggests a previously unknown mechanism behind the function of LL-37 and similar peptides, which are being tested in early-stage clinical trials for treating infections resistant to classical antibiotics. A better understanding of how antimicrobial peptides work could help researchers develop them into therapies.

Using advanced microscopic techniques, Weisshaar and his graduate students Yanyu Zhu and Soni Mohapatra have documented the stopping power of LL-37, an antimicrobial peptide made by the human immune system as a first-line defense against pathogens. LL-37 belongs to a class of ancient peptides that fight bacteria in a different way than most other antibiotics, one that is difficult for bacteria to resist. But the mechanism behind the action of LL-37 and its kin has been hard to pin down.

Proceedings - National - Academy - Sciences - January

Writing in the Proceedings of the National Academy of Sciences in January, Weisshaar's group reveals that once LL-37 gains entry to a bacterial cell, it rapidly impairs the freedom of movement needed for DNA and proteins to work. The researchers speculate that LL-37's large positive electric charge helps it bind to the overwhelmingly negatively charged molecules within the cell, making the damage permanent.

Most antibiotics are small-molecule chemicals that work by interfering with...
(Excerpt) Read more at: phys.org
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