17 December 2007

Creationist Resistance to Antibiotic Resistance, Part I

Earlier last week, GilDodgen of Uncommon Descent wrote about his plans to revolutionize medicine and save us all from antibiotic-resistant bacteria. He exhibits some spectacularly BAD logic, even for a cdesign proponentsist. For a few excellent takes on WHY he is so stupid, check out these fine bloggers:
Humble Monkey
Sandwalk
Respectful Insolence
Panda’s Thumb
ERV

Now, I don’t want to go into Dodgen’s points and claims specifically; those have already been torn to ribbons in the links above. Instead, I want to address the more general trend of creationist denial regarding antibiotic-resistant bacteria.

Resistance to antibiotics (henceforth just “resistance”) is one of the starkest examples we have of the power of evolution by natural selection of random mutation. So it only stands to reason that creationists will fall over each other to deny that resistance has anything to do with evolution. To do so, they employ two main talking points lies (embodied in this *shudder* Answers in Genesis article):

1) “The genes for resistance are not the result of random mutation; they’ve been there all along, we just didn’t notice them!”

2) “Even if resistance DOES occasionally result from random mutation, it doesn’t count as evolution, because there’s always a price to be paid for gaining resistance.”

We’ll deal with that first lie today.

Even if the creationist grudgingly admits the importance of natural selection to the growth of a resistant population, they vehemently deny that what’s being selected is the result of random mutation. Instead, they say that either there were a handful of resistant bacteria around to begin with, or they inherited the genes for resistance from a different kind of bacteria via lateral gene transfer. Dodgen’s post falls into this camp, sort of, since he’s downplaying the power of random mutation. Another, perhaps clearer, example would be a recent UD post by idnet.com.au discussing divergence of E. coli in the human gut versus that of the baboon. Although resistance is not specifically addressed, it is claimed that any new genes found in either population of bacteria must be the result of lateral gene transfer.

ResearchBlogging.orgReal science, of course, is chock FULL of examples of the power of random mutation. Let’s look at just one example: Pseudomonas aeruginosa infections in patients with cystic fibrosis, from a paper published by Antonio Oliver et. al. in the journal Science in 2000.[1] (See that little BPR3 icon? That’s the sign that things are about to get good.)

Cystic fibrosis (CF) is a genetic disorder resulting from a mutation in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). Normally, CFTR adjusts ion concentrations in order to make water flow out of the cell via osmosis. In the lung, this source of water is what keeps your mucus nice and wet and fluid. But if CFTR is broken, the mucus in the lung (and elsewhere, such as the GI tract) becomes dry and super-thick, causing all kinds of hell for the CF patient’s body.

P. aeruginosa is an opportunistic bacteria; it can't and won't infect a healthy adult. It can, however, cause serious infection in certain scenarios if exposure is high and the host's defenses are already down. Two major targets for serious acute (short-term) infection are mechanically ventilated patients and victims of serious burn wounds. But for patients with CF, P. aeruginosa instead causes chronic (long-term) infection. For most such patients, it’s not the CF that kills you, it’s the Pseudomonas.

As it turns out, P. aeruginosa infections from CF lungs show a lot more colony diversity than colonies grown from patients with acute infections. Oliver’s group hypothesized that this diversity was due to the conditions within the CF lung, which as a result of hyperosmolar viscous mucus is highly compartmentalized and continually changing. Such an environment would favor the growth of bacteria that could keep on their toes, so to speak, quickly and readily adapting to changing environmental niches within the lung. And evolutionary biology predicts that, in order to adapt to that kind of environment, you have to be really good at mutating.

So the experimenters collected a whole bunch of P. aeruginosa samples from 30 CF patients, and a whole bunch of P. aeruginosa samples from 75 patients with acute infections, and compared the mutation frequencies of those isolates. Both the CF and non-CF patients had a whole bunch of P. aeruginosa isolates with low mutation frequencies. But in addition, the CF patients had a whole bunch of isolates with mutation frequencies 100 times as great! Genetic analysis of these mutator isolates over several years indicated that they were all different and persistent; these were bacteria that evolved into mutators within the host and stuck around, and not mutators transmitted between patients. Further investigation demonstrated that, for several of the mutator isolates, one or more error-avoidance genes were mutated or deleted altogether, explaining their high mutation rate.

This is the point in the presentation when a creationist might say, “Aha! Nothing new was created; mutation was only capable of breaking genes that were already there!” But this is only the first half of the story; as we’ll see, the mutator phenotype opens the doors to further beneficial mutations.

You see, cells normally keep those error-avoidance genes around for a reason. If the mutator phenotype is so prevalent in CF patients, it must be conferring some advantage in that environment. That is, given the conditions of the CF lung, it’s apparently more important to be able to get beneficial mutations than to prevent detrimental ones.

Patients with P. aeruginosa infections, especially those with CF, are subject to extensive treatment with a broad range of antibiotics. So the experimenters took a look at whether the mutator phenotype had any effect on the evolution of antibiotic resistance:



This is the key figure for our discussion. In case you can’t tell, black bars are mutator strains from CF patients, grey bars are non-mutator strains from CF patients, and white bars are strains from non-CF patients (all non-mutator). For a broad range of antibiotics, mutator strains showed a much higher frequency of antibiotic resistance compared to non-mutator strains.

The only way this makes sense is if antibiotic resistance is the result of naturally-selected random mutation. Mutator strains have higher mutation rates, and are therefore more likely to acquire the mutations necessary for resistance. The non-CF non-mutators serve as a control. The important comparison is between CF mutators and CF non-mutators, because they had everything in common except their mutation rate. They were derived from the same ancestral strains that first infected the patient. They were subject to the same antibiotic therapies. They grew in the same environment, shared space with the same other species of bacteria, and therefore had the same potential for lateral gene transfer. If resistance were the result of anything other than mutation, then we should see no statistical difference between the black and grey bars. But we do see a difference.

That’s evolution. The CF lung is a dynamic environment with different selective pressures than sites of other, acute infections. CF lungs favor selection of bacteria that can mutate rapidly. This increased rate of mutation results in other selectable beneficent mutations, such as resistance to antibiotics.

It’s important to note that Oliver and company weren’t trying to convince anyone that bacteria evolve; real scientists understood that already. They were trying to use that understanding to save people’s lives. Their insight into how a Pseudomonas infection behaves within the lung is the first step to fighting that infection. Armchair physicians who don’t understand antibiotics and deny the power of random mutation are of no help to the dying.

Next time we’ll look at that second creationist claim, and what random mutation can do to bacteria that are already resistant to antibiotics. That’s when things get really intense.

Resource:
[1] Oliver, A. (2000). High Frequency of Hypermutable Pseudomonas aeruginosa in Cystic Fibrosis Lung Infection. Science, 288(5469), 1251-1253. DOI: 10.1126/science.288.5469.1251

2 comments:

-DG said...

Hi, I just came across your blog after someone linked me to your Poe's Law post and just started reading through. What irritates me when Creationists jump on this point that you refute is that Lateral Gene transfer is actually one of the primary mechanisms of evolution in bacteria, and there is currently some debate as to whether mutations or transfer are more important.

Of course mutation is still around, and it is how resistance to newly invented antibiotics pop up. Resistance genes that work on a similar (in some way) type of antibiotic tend to acquire mutations and through selection adapt to this new antibiotic. Then, through lateral transfer, can be more easily spread to other bacteria within the colony. Or that one mutated bug may simply grow faster and a selective sweep happens whereby it takes over the colony as the rest die out due to the antibiotic.

LGT doesn't imply that those genes were always present, they came from somewhere. And in fact we can use transfered gene cassettes from different species and groups of bacteria to look at how they have evolved.

Good post, and a wonderful explanation of the paper. I thoroughly enjoyed it.

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