The Bacterial Good Samaritan

Sep 07 2010 Published by under Evolution, Physiology/Pharmacology

So we are now headed off to a new, shiny server which will hopefully make us all happy and responsive again! And what better way to start it off than with a paper that BLOWS MY MIND?!?!

I'll admit that Ed actually blogged it before me (though I had intended to blog it for a while), and so at first I thought I'd leave it alone, but then Ed and Razib put on the peer pressure to have me blog it, too. I'm a doormat for those guys. 🙂

But really, it's a great paper to blog. When I first looked at it, I thought "oh, maybe it's your basic viral gene transfer and they got it looking all nice". But when I saw the specific mind was blown that much more.

So here we go, let's talk about some antibiotic resistant bacteria. Lee et al. "Bacterial charity work leads to population-wide resistance." Nature, 2010.

I'm sure you've all heard about antibiotic resistance in bacteria. Really basically, this results from evolution in action (insert action music). When you give antibiotics to a pile of bacteria, you run the risk of a few of them having mutations which make them resistant to that antibiotic. So rather than getting killed, they can make it, and keep reproducing. Because they keep reproducing (and with their less resistance brethren around, it means they have more space and resources to reproduce into), you end up with larger populations of bacteria that are resistant to antibiotics. This is obviously a problem, because it means that bacterial infections that we could formerly treat easily are now VERY difficult to fight.

But when bacteria grow resistant to an antibiotic, do the non-resistant mutants ALL die out? Apparently not. And the paper wanted to know WHY.

So they exposed a colony of your basic E. Coli to the antibacterial drug norfloxacin (an antibiotic used to treat things like urinary tract infections). They carefully measured the dose of antibiotic so that roughly 60% of the bacteria would kick it in each bacterial culture. You might think that this wouldn't be very useful to kill the infection, and indeed it's not. What they wanted to see was how the bacteria populations evolved and changed over time as a population, rather than as single bacteria.

Sure enough, as has been seen loads of time by now, the colonies developed resistance to the antibiotic. But the scientists noticed something interesting. When they took individual cells out of the population and looked at them, they saw that they had a few bacteria that were REALLY resistant to the antibiotic (highly resistant isolates or HRIs). What was surprising was that MOST of the bacteria were NOT really resistance to the antibiotic! They were Less resistance isolates (LRIs), and somehow, they were still making it by being associated with their HRI buddies.

So what was causing this sharing of antibiotic resistance? It turns out the resistant cells were producing lots of indole. Indole is a compound that is naturally produced by growing, healthy cells. But it's got a role to play, it is a chemical signal to other bacteria in the area to harden the f**k up.

(My name is indole, and I'm telling you that Bacteria need to harden the f**k up)

In the presence of indole, bacteria will increase production and activity of drug-efflux pumps (which can then pump the antibiotic out of the bacterial cells), and will also turn on mechanisms to protect the bacteria from oxidative stress. Normal, healthy cells produce indole. Dead and dying cells do not.

But what is it about those few hardened up indole producing cells that allows them to survive? Well, it's not the indole itself. Instead, it's the resistant bacteria. They had mutations which allowed them to survive, producing more drug-efflux pumps and resisting chemical damage. Then those cells, which had the hardcore mechanisms allowing them to be healthy, produced indole like normal healthy cells, telling the non-resistant cells to harden the f**k up.

The model they developed looks like this:

The far left is a section of normal, healthy cells. You can see they are all producing indole (in green). The middle panel is cells under stress from an antibiotic (in red). There is no green indole to be seen because the red cells are dead or dying. In the far right, though, a resistant bacteria comes on the scene. He feels just fine and starts producing indole again. Cells in the vicinity pick up on the indole signals and push the antibiotic out. The resistant cell is protecting his neighbors.

But this isn't all free and dandy for the resistant cells. Pumping out indole actually does take energy, and so the resistant bacteria have a COST to helping the cells around them. The authors hypothesize that this is actually bacteria level kin selection. Because bacteria reproduce asexually, all the bacteria share highly similar genes with each other. So the resistant bacteria has a vested interest in protecting her kin, who may then develop other beneficial mutations as a result of being able to stay alive. You could even call it a form of altruism.

Sci thinks this is all incredibly cool, but she does have one question. If a normal, healthy cell produces indole anyway, and the resistant bacteria are producing indole because they are resistant and therefore normal and healthy in the presence of antibiotics, why does producing indole have a cost for these bacteria? I mean, maybe producing indole ALWAYS has a cost, and if it does, why would it have MORE of a cost in these drug-resistant bacteria? It's not addressed in the paper (not that they necessarily could, it's only four pages, as required by letters to Nature, which Sci thinks is rather foolish and not necessarily to their benefit, as they then put every flipping thing into the supplementary material, but that's a rant for another time), but does anyone know? Any microbiologists out there know about indole production? I think that'd be some good follow up. How much does kin protection really cost?

Lee HH, Molla MN, Cantor CR, & Collins JJ (2010). Bacterial charity work leads to population-wide resistance. Nature, 467 (7311), 82-5 PMID: 20811456

7 responses so far

  • VMartin says:

    Yeah, the whole problem of antibiotic resistance is pretty complicated and there remains a lot to be explained.

    "I’m sure you’ve all heard about antibiotic resistance in bacteria. Really basically, this results from evolution in action (insert action music).

    I don't see any "evolution in action". E.Coli hasn't probably changed for millions of years and therefore there is no need to see here "evolution in action".
    In other case also breeding of dogs can be also hailed as "evolution in action". Actually some bacteria might have had some apparatus which turned out to be advantageous in a given moment .

    "How much does kin protection really cost?

    All these "inclusive fitness" and "kin selection" concepts seem to be pure speculations and nothing else. There are also a lot of speculative math behind these concepts, but as far as I know no one has defined exactly this "cost". We know gravitational constant, Planck's constant etc... but this hausnumero "cost" is so volatile than no one has caught it yet. It's more a matter of believe as insect eusociality shows clearly.

  • razib says:

    i was gonna respond to #1, and then noticed that he's got "non-darwinian views on evolution." lol.

    great post. i gotta integrate youtube and other media into my posts. i sometimes feel like i'm channeling an 82 year old british dude when i do peer reviewed blogging.

  • yes says:

    yeah, razib. put her good link on your delicious thing cuz sometimes i forget to come here. awesome post!

  • Vicki says:

    If you're unhappy with evolution because things aren't "well enough" quantified, look up the precision, or lack thereof, with which we know the gravitational constant G.

  • Adrian Blake says:

    Altruism and kin selection in bacteria? I totally just nerdgasmed! Great post, n yeah the first comment did confuse me until I realised that THEY were confused. Keep up the good work!

  • Henry Lee says:

    Thanks for the great blog post! I've got the pic up at my bench... wish I could tack the video on my bench too...

  • Lab Rat says:

    " E.Coli hasn’t probably changed for millions of years"
    Um yes it has. E. coli has changed a *lot* in the last millions of years, in fact because of the short generation time and high mutability, bacteria have changed more than any other species. Over the last million years the bacteria that eventually became E. coli have changed their resistance, their ability to conquer different habitats, the acidity they can deal with, their DNA-sharing abilities, and probably some of their metabolic abilities as well.

    Don't make the mistake of thinking bacteria don't change just because you think they look the same. Metabolically and biochemically that is a buzzing little organism.

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