Wednesday, July 15, 2015

A World From Dust (Plus): Why Pepto-Bismol Kills Bacteria but not Humans

Chapter 2 of A World From Dust explains how Pepto-Bismol works. That pink stuff kills ulcer bacteria because of its chemistry -- the bismuth in it is so sticky that it sticks to and jams up proteins in bacteria.

The sharp-eyed reader will notice that a key part of this story is left out. Human and bacteria proteins have the same basic chemistry, being made of the same CHON atoms. If bismuth is sticky to bacterial proteins, it must be just about as sticky to human proteins. So if bismuth kills bacteria, it should kill human cells as well. So why is it that we can drink the stuff? Why is there a novel titled Arsenic and Old Lace but Bismuth and Old Lace doesn't scare anyone?

Human cells can survive a dose of Pepto because they have an extra layer of chemical protection. Our internal chemical shield is built from sulfur, in the form of the molecule glutathione, mentioned in another part of Chapter 2. How this shield works is shown in a 2015 PNAS paper titled "Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells" (which, incidentally, is so well done that other scientists would do well to pattern their metal-life investigations on it).

As shown in the diagram above, purple bismuth (Bi) approaches from the left. It crosses the cell membrane and sticks to yellow glutathione's (GSH's) sulfur atoms. Bismuth is so sticky it collects multiple glutathiones, then the cell takes the assembly and tucks the dangerous metal away into a small sulfurous bubble (or vacuole) shown in gray on the right. This is what glutathione is for -- to preemptively stick to the sticky things before they can stick to something else.

The really nifty part of this is that as this process depletes glutathione, the cell senses that and turns on the machinery for making more glutathione. The more bismuth abounds, the more glutathione super-abounds to fix it. Excess glutathione is then available for sticking to other toxic metals as well, so that Pepto may incite a more general protection.

The bacteria killed by Pepto-Bismol don't have a complex glutathione system like this, so its stickiness turns their insides to solids, and they die. Human cells can resist internal petrification because of the chemistry of sulfur as corralled by glutathione's structure. Our cells sweep the sticky bismuth into a side chamber and our proteins remain nice and fluid.

This has implications for cancer therapy. Some forms of chemotherapy kill cancer cells with sticky, toxic metals like platinum. Cancer cells resist the chemo by turning up their glutathione production. Understanding how that system works should allow us to find a way to turn it off, which would make metal-based chemo much more effective. More details can be found in this summary article related to the research article above.

This is also why understanding the chemistry is so helpful. Bismuth-sulfur chemistry may lead to more effective chemo. So support your neighborhood chemist -- you never know what she'll find next.

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