I'm very excited about this post, which is a guest post from my sister! She's an undergrad doing biochemistry at Bristol University, and she's currently taking a year working in a research laboratory as part of her degree. She's working with Plasmodium at the moment (which is the little protist that causes malaria) but has sent me a bacteria-related post because she knows me, and she knows my blog and who doesn't love bacteria?Bacteria have always been very adaptable when it comes to surviving evolutionary stressful situations, such as exposure to antibiotics. Usually some form of mutation will arise leading to the creation of resistant strains of bacteria. These will be selected for via ‘natural selection’ processes and go on to replicate to produce a whole population of resistant bacteria that are able to survive.
However new research looked at a colony of wild type E.coli bacteria in a bioreactor under exposure to increasing levels of the antibiotic norfloxacin and found that no more than 60% of growth was inhibited to maintain a sizable population. The resistance levels of the population as a whole, and of 12 random individuals, was checked every day and it was found that they did not correspond to one another.The majority of the individual isolates were less resistant than the population as a whole but there was one mutant found that was highly resistant. By isolating the supernatant from the high resistance individual, and conducting gel electrophoresis to separate out the intracellular components, a protein was found that was produced in very high numbers.
This was the enzyme tryptophanase which has the main job of breaking down tryptophan to ammonia, pyruvate and indole. Experiments were done to show that the third molecule, Indole, provided an obvious survival benefit under antibiotic conditions. It upregulated multi-drug efflux pumps which helped in the physical export of the drug and it also had a role in activating various oxidative stress protective mechanisms. The mass production of Indole by the highly resistant mutant allows more vunerable cells in the surrounding area to survive.
b) dead and dying bacteria fail to produce indole
c) mutant appears and supplies indole at a fitness cost to itself.
The resistant bacteria is therefore not selfishly replicating to outgrow the rest of the population but, in helping others to survive, is enduring a fitness cost of its own by mass producing Indole.
This experiment was also carried out using various different antibiotics and the same bacterial altruism was found to exist. The survival of the weaker bacteria does have some advantages as it allows further exploration of mutations that could be even more beneficial to the population. Also, it keeps the opportunity for the bacteria to return to their original state if the stress is temporary, rather than keeping up the energetically wasteful production of antibiotic resistance genes.
So, bacteria working as a team to ensure not just temporary survival but long term advantages for the whole population. Not just survival of the fittest.
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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 comments:
If such a strategy of adaptation has long term survival value, you could still call it survival of the fittest. A product of the evolution of better evolution.
This makes quite good sense. If I understand this correctly, only a small number of actually resistant bacteria are necessary to produce the enzyme that gives a population-wide protection.
It is therefore not necessary for the resistant variant to become dominant in the population in order to receive the benefit. In fact, since the resistant variant is less productive than the non-resistant, using part of it's energy to produce the enzyme, it is expected that they should not become dominant.
So, once a certain percentage of resistant bacteria are present, there is a population-wide protection and the non-resistant bacteria, which are more efficient, dominate. If the percentage of resistant bacteria is higher than this magic number, the antibiotics are not effective and the non-resistant variant out-competes the resistant variant.
On the other hand, if the percentage of resistant bacteria fall lower, the population-wide protection fails and the non-resistant bacteria will die in much larger numbers, increasing the proportion of the resistant variant.
I'd expect there to be a fairly stable fraction of resistant bacteria. Is that what you found?
Oops, I'm a doofus. You're not describing your own work.
*feeling stupid*
I'll just go read the article, then.
The thing I found interesting, and why it's titled 'survival of the fittest?' is that while obviously it gives a long term survival value to the bacterial population it doesn't give survival value to every individual bacteria. The resistance depends not on every cell being capable of surviving the defence.
Lucas: heh :p From reading the paper it does seem that the fraction of resistant bacteria is very stable. However you are forgetting one important fact in your model - bacteria can communicate...
Nice post lab rat sister! You should write more and grow a blog ;).
Concerning your response to Lukas' question (I, confusingly, had the same question), did the researchers try to show that this is not simply population dynamics, and indeed 'teamwork via communication' that gives the resistance?
Interesting, if a little depressing from the human context: the little blighters are far too hard to get rid of.
I was also struck by the seeming lack of advantage to the individual bacterium. Is it just the case that when bacteria produce enzymes they're inclined to churn them out in large numbers? Seems unlikely, as it's inefficient.
Or is there some advantage to being part of a large population?
@CUCO3: Just churning out enzymes would be highly inefficient, and bacteria are far too well organised for that! There are, however, many advantages to being in a large population. It makes you less likely to be killed by the immune system, it's easier to colonise places, with some bacteria large populations allow them too form a biofilm, which keeps the bacteria within it *very* safe and is a major problem for antibiotics).
@Lucas (sorry for the late reply I thought I'd answered this): even population dynamics would not explain why only a stable and relatively small section of the bacteria showed full antibiotic resistance. Whether signalling is involved is another matter of course, but it wouldn't surprise me if a signal molecule of some kind was found to play a part.
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