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Rewiring Bacteria

Earth is basically a bacteria planet, despite humankind’s naked-eye-level profile. They’ve been here unfathomably longer than we have, they live in plenty of places where we can’t survive, and their biomass far outranks ours. This paper will show you just how adaptable the little creatures are. Wild-type E. coli (like many other bacterial species) can synthesize all its essential metabolites and cofactors from scratch (unlike us, for example, having to get several vitamins from our diet). These pathways have been worked out in some detail. For example, it’s known that aspartate 1-carboxylase (known as PanD) is an essential enzyme for the synthesis of beta-alanine. In turn, beta-alanine is essential for the synthesis of pantothenate, which is essential for the synthesis of Coenzyme A, which is essential for life itself. So what happens if you delete the PanD enzyme? All the bacteria just plotz, right?

Well, disrupting a direct pathway tied to an enzyme essential for all life on Earth is a challenge. You can generate that PanD mutant just fine, and they’ll grow happily as long as the culture medium contains beta-alanine to keep them going. The authors gradually diluted that out, though, and put the bacteria under strain to see what would happen. I have to admit that the colony of wild-type bacteria used in the study weren’t up to the challenge, and did not mutate out of the problem. But giving them a higher propensity to throw off mutations by compromising DNA proofreading gave some results. That’s the sort of mutation that normally could be troublesome for any given bacterial population, but comes in quite handy under unusual conditions, and in fact many types of bacteria are known to increase their mutation rate under stress.

Speeding things up in the manner gave a number of varieties that worked out a way around the lack of what had been essential beta-alanine supplies. One pathway that emerged did so by degradation of uracil. Interestingly, this didn’t involve changes to any enzyme structure or function, but rather in expression levels of existing ones. The mutations showed up in various repressor proteins, and allowed more uracil to be synthesized and more of it to spill over into a pathway that could generate beta-alanine, through an intermediate (malonyl semialdehyde) that’s normally considered toxic, but in this case got immediate converted to the desired product. This uracil pathway turned out to be a popular one. The group took the 11 strains that had evolved a way out of the beta-alanine stress and deleted a key enzyme in this pathway (RutABC), and that wiped out all but three of them – so in whole or in part, chewing up uracil was an attractive solution.

What if you delete both PanD and RutABC? That forces the bacteria to tap-dance even faster, but they’re up to the challenge. Under those conditions, the survivors turned out to all have the same mutation as evolved in the three leftover strains in the experiment above: they all changed G655 in ornithine carboxylase (SpeC) to either serine or alanine. This allowed the enzyme a wider scope for a decarboxylation/deamination reaction (while actually limiting another decarboxylation pathway, so there’s a tradeoff for survival). OK, what about a triple mutation? Take out PanD, RutABC, and SpeC all at the same time? The bacteria even found a way out of that corner, Houdini-style. This pathway isn’t completely worked out, but mutations appeared in arginine decarboxylase (SpeA), S-adenosylmethionine decarboxylase (SpeD), and spermidine synthase (SpeE).

These sorts of studies have been done with other nutrients and enzyme pathways, but this is the most detailed look at the adaptations that I’ve seen. It’s clear that there’s a lot of biochemistry that can be repurposed under this kind of severe pressure (betting against bacteria is like going in against a Sicilian when death is on the line). It’s important, though, to remember the problem of teleology here: it’s easy to talk about things in terms of their purpose (and that’s what I’ve been doing), but that makes it sound like that bacteria are planning their moves. They’re not, of course.

These are error-prone organisms (that was a human purpose, as described above). So there are uncounted mutated strains present in the culture; every single cell in the vial is probably a different beast. As you start to decrease the amount of beta-alanine available, the story isn’t about a wily bacterium coming up with ways to counter the problem – it’s about everything else in the culture dying because they can’t make it under the new conditions. Whoever is left gets to divide again, spinning off still more mutations, some of which will turn out to be able to deal with the next round of shrinking beta-alanine levels, and most of which won’t. What you get at the end is a particular pile of accidents that managed to hang together, survive, and reproduce. I’m one of those, too, and so are you.

16 comments on “Rewiring Bacteria”

  1. Hap says:

    But can they fight a land war in Asia?

    1. Derek Lowe says:

      Hah! I’d argue that Y. pestis did. . .

      1. John Wayne says:

        No more rhyming now, I mean it!

        1. myma says:

          Anybody want a peanut?

          1. Murphy says:

            This little thread brought an unreasonable amount of joy to my day.

  2. JSR says:

    But can those “evolved” strains compete against wild-type strains? Almost certainly not.
    These exercises are interesting, but they’re like identifying a breed of poodle that can walk around on its hind legs. It’s interesting, but an evolutionary dead end, because if you limited resources and put the bipedal poodles against 4-walkers, the 4-walkers will quickly take over.

    1. truthortruth says:

      It depends on the environment. The power of this study is to show what could be, not what is today.

    2. a-non says:

      If you want a more “practical” mutant, you can look at the e. coli long term evolution experiments. The ability to do aerobic growth on citrate is clearly a benefit over the wild type (at least, in an environment where citrate happens to be present).

    3. hn says:

      Many of us are not so interested in the bacteria per se but the biochemical pathways, biosynthetic enzymes, and their adaptability.

    4. Old Pump Kicker says:

      In the wild, bacteria that are viable but not optimally fit don’t totally die out. They will survive as a minority population, ready to take over if the environment changes. That’s how antibiotic resistance (for example) hides until it’s useful.

    5. David Edwards says:

      You’re missing the point. Namely, that the wild type strains will compete better than the mutants, when placed in the typical wild type environment, because, well, duh, that’s what the wild type bacteria evolved to live in. The moment that environment changes, however, the current wild type bacteria could suddenly find themselves less fit than the mutants. Fitness is always relative to the environment, and when the environment is dynamic, so is fitness. This is, or should be, one of the elementary lessons taught in Evolutionary Biology 101.

      Consequently, experiments that investigate what happens to organisms when the environment is changed, both wild type and controlled mutants, are perfectly valid generators of proper evolutionary conclusions.

  3. Jeff says:

    You might be tired if you misread “Wild-type E. coli” as Wile. E. Coyote. Or maybe its the reading glasses from Acme.

    1. DH says:

      That is exactly how I read it on the first pass. It stopped me in my tracks with a, “Wait. What?”

  4. luysii says:

    “Earth is basically a bacteria planet, despite humankind’s naked-eye-level profile. They’ve been here unfathomably longer than we have, they live in plenty of places where we can’t survive, and their biomass far outranks ours. ”

    Not only that, they’ve probably been making petroleum deep underground while oxidizing H2 —

  5. Li says:

    Algae and their descendants (plants) far outmass bacteria, so I’m voting for them. Certainly it can easily be argued that Earth is basically a C3 plant planet.

  6. Neil Readwin says:

    If you knock out a primary pathway to a required molecule, and life survives, then I would credit evolution with having backups. In some cases evolution provides multiple backups.

    Are molecules with more favourable metabolites favoured?

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