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Bacterial charity – the bad kind

September 3, 2010

Antibiotics are awesome. They can be credited with saving more human life than any other invention and have been one of the best advancements in public health second only (maybe) to sanitation. But, as with all things pathogen related, the microbes are fighting back. Antibiotic resistance is on the rise, and diseases like MRSA (Methicillin-resistant Staphylococcus aureus) have been making the rounds in hospitals and causing a significant number of deaths.

Antibiotic resistance arises due to random mutation and natural selection. If there are a few hundred billion bugs in an infection, and even one has a slight growth advantage in the presence of an antibiotic, that bug will divide, pass on it’s beneficial mutation to its offspring while the less fortunate die off, and open the door for even more mutations and increased resistance down the road. At least, that’s what we thought.

But a new paper in the journal Nature shows that the resistant strains can actually cooperate with each other to increase the resistance of the whole population:

This work establishes a population-based resistance mechanism constituting a form of kin selection whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.

These researchers took a strain of bacteria that was sensitive to the antibiotic norfloxacin. They gave the population a sub-lethal does of the antibiotic (it slowed them down, but didn’t kill them entirely), and watched resistance develop. After a few days, the bugs were able to grow at a normal rate. So they upped the concentration of antibiotic, and and watched as the bugs devised new ways of fighting it.

The little green dotted lines show the concentration of the antibiotic as the stepped it up over the course of a couple weeks. The red line shows the resistance of the total population, and it increases with a slight lag behind when the dose is increased. That part isn’t all that surprising – we know bacteria can evolve pretty quick. The interesting part is that they took individual bacteria out of these cultures and assessed how good they were at resisting norfloxacin. If the model I talked about in the beginning were true, you would expect only the most resistant individuals to survive, and the rest to fall by the wayside. And you’d expect each individual to have the same resistance as the total group. But that’s not what they found.

Look at the grey bars in that graph – those represent the resistance levels of individual bacteria pulled from the main culture. Each individual isolate they pulled had a far lower resistance than the population as a whole. This means that the bacteria must be cooperating with each other in order to survive. Cooperation amongst bacteria isn’t a new idea, but this is the first time that it’s been directly shown with respect to antibiotic resistance. I’m not sure this research necessarily helps us design better antibiotics or prevent resistance, but it’s an important reminder that the bugs are pretty smart – we need to be smarter to defeat them.

4 Comments leave one →
  1. September 4, 2010 7:28 am

    Wow! this is really exciting research, thanks for covering it. I did do some work once using sub-inhibitory antibiotic concentrations to increase bacterial secondary metabolite concentrations, and I know that you can create resistant mutants by growing on antibiotics, but I’m intrigued by the idea that certain bacteria go deliberately haywire in order to help the rest of the colony.

    That could work with some kind of quorum sensing signalling though; like some kind of signalling version of pulling straws.

    (btw…if you haven’t already I would consider applying to join It’ll aggregate all your science posts, and you already fill the criteria to get in)

    • Kevin permalink*
      September 4, 2010 8:55 pm

      Thanks for the suggestion – I just put in my application 🙂

  2. James permalink
    September 5, 2010 2:53 am

    Nice post. I wonder how well this apparent cooperation would work in vivo? Conditions in a bioreactor are very different to the nasopharynx where you would find S. aureus. Is there any suggestion these results could be replicated in vivo?

    • Kevin permalink*
      September 5, 2010 2:32 pm

      It would probably be difficult to control for exact antibiotic concentration, but I’m sure this is the next step. Maybe they could culture the infection in vivo and then just test for total resistance and individual resistance ex vivo.

      We know antibiotic resistance occurs, and if they can cooperate, I’d be surprised if they don’t cooperate.

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