Zoology to the Rescue

Saturday, September 19th, 2015

Zoologist Adin Ross-Gillespie of Zurich University applied some evolutionary thinking to drug resistance:

One of these [cases where the survival of the fittest cannot easily occur] is related to the way many bacteria scavenge a crucial nutrient, iron, from the environment. They do it by releasing molecules called siderophores that pick up iron ions and are then, themselves, picked up by bacterial cells. In a colony of bacteria, siderophore production and use is necessarily communal, since the molecule works outside the boundaries of individual cells. All colony members contribute and all benefit.

In theory, that should encourage free riders — bacteria which use siderophores made by others without contributing their own. In practice, perhaps because the bacteria in a colony are close kin, this does not seem to happen. But inverting free riding’s logic makes the system vulnerable to attack, for a bug that contributes more than its share does not prosper.

Following this line of thought Dr Ross-Gillespie turned to gallium, ions of which behave a lot like those of iron and can substitute for them in a siderophore, making it useless to a bacterium. In fact, siderophores bind more effectively with gallium than with iron, hijacking the whole process. A judicious dose of gallium nitrate can thus take out an entire bacterial colony, by depriving it of the iron it needs to thrive.

The crucial point is that, because siderophores are a resource in common, a mutated siderophore that did not bind preferentially to gallium would be swamped by the others, would fail to benefit the bug that produced it, and therefore would not be selected for and spread.

[...]

As they expected, both the antibiotics and the gallium nitrate curtailed the growth of Pseudomonas to start with. As they also expected, resistance to both of the antibiotics built up steadily over the 12-day course of the experiment. But nothing similar happened in the cultures exposed to gallium nitrate. These continued to be suppressed. And when the researchers took a closer look at what was going on, they found that not only were the bacteria in their gallium-laced samples starved of iron, but the bugs were also responding to the crisis by pouring their energy into producing more and more siderophores, thus hastening the colony’s demise.

What makes all this more than just a laboratory curiosity is that gallium nitrate is already an established drug.

Comments

  1. Alex J. says:

    That’s pretty sweet.

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