[This post was originally published at webeasties.wordpress.com]

The best defense against pathogens is to never let them gain access to our delicious, gooey insides. Our skin is pretty good for this purpose: it’s pretty tough and mostly impermeable, and the only way most of our surface tissues can get infected is if that skin barrier is broken. But we can’t have skin everywhere. Our airways and digestive tract have to be permeable so that we can absorb air and nutrients. In our gut, we can’t have skin, but we do have tens of trillions of commensal (friendly) bacteria that colonize us, and they can generally out-compete the bad bugs that want to do us harm.

But when those barriers are inevitably breached, the immune system throws up other defenses. The presence of bugs where they’re not supposed to be triggers inflammation – a whole host of responses that recruit immune cells, trigger release of nasty chemicals, and generally makes the tissue an inhospitable place for anything to grow and divide. Commensals, for some reason that we don’t fully understand, don’t generally trigger inflammation, and so we have a happy co-existence. They keep the bad bugs out, and we don’t try to kick them out. Enter Salmonella:

Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate.

In order to get a leg up on the competition, Salmonella evolved a way to actually benefit from inflammation. One group of nasty chemicals that the immune system produces are called reactive oxygen species. As their name suggests, these chemicals react with all kinds of stuff, screwing up lots of biological molecules and making all kinds of organic by-products. Salmonella manages to use one of those products in a novel way – to carry out respiration, allowing it to out-compete all of those commensals that are supposed to be acting as a shield.

There’s very little oxygen in the gut, so most gut bacteria are anaerobic. But anaerobic metabolism isn’t particularly efficient – a lot of the energy potential in every unit of food is wasted – so Salmonella learned to use tetrathionate instead of oxygen to carry out respiration. That way, they can grow more using less resources than the commensals. Usually, blocking the production of reactive oxygen species makes infections worse, but these researchers found that it actually rendered Salmonella less infectious.

And this is why we will never defeat the microbes: even our best immune defenses get subverted and turned into an advantage for pathogens.


  1. #1 objecpers
    November 2, 2010

    Microbes are far simpler than humans in that one individual microbe consists of far fewer interacting components. This allows them to evolve much more rapidly simply because they have fewer components to act on, meaning that a mutation in one component of a microbe has a much greater impact on the microbe as a whole than does a mutation in one component of a human. This is why there is a much greater diversity of microbes (in particular bacteria and archaea) than “higher” organisms such as vertebrates (including humans). This is also what leads to this evolutionary arms race between humans and their microbial inhabitants. I think it is also important to point out here that many of the “friendly” microbes living in and on our body can turn not-so friendly given the right conditions, such as an excess of iron in our bodies, which is a common limiting nutrient for microbes living in our bodies. In fact, our body has numerous mechanisms to bind up iron and prevent microbes from using it, because of this.

  2. #2 Kevin
    November 2, 2010

    Yes, this is all true. Bacteria (and viruses) win because of there simplicity. Thankfully for us, it’s not to the microbes benefit to kill us all off, otherwise we would likely be dead.

  3. #3 sinz54
    November 2, 2010

    Actually, our skin has “normal flora” colonizing it as well. And just as in our gut, this normal flora helps outcompete pathogens.

    And the bacteria in our gut aren’t just commensal. They help us absorb fluid and vital nutrients from our food. In return for which they get to eat their share. It’s a true symbiotic relationship, one that goes back a long way. (I’m sure that Dimetrodon depended on it too.)

  4. #4 Kevin
    November 2, 2010

    sinz54 – Absolutely. Usually, we use the term “commensal” to talk about ALL the microbes that colonize us but don’t do any harm. They’re definitely on our skin, but also in our mouth, nose, aural cavities, genital tracts – basically any place that’s exposed to the outside world.

    Many are symbiotic, for sure, and there are probably many that just hang out and don’t do any harm or provide any benefit. We’re just starting to plumb the depths of their diversity.

  5. #5 pworthen
    November 3, 2010

    Is this a case of “he who evolves the fastest wins”?

    But, if that were the case, how would multicellular organisms have ever flourished in the first place?

  6. #6 Kevin
    November 3, 2010

    @ pworthen – Yes.

    The answer to your second question is a bit more nuanced, but the short answer is that it’s beneficial for the microbes for multicellular organisms to flourish. It’s a common misperception that all infectious bacteria/viruses etc would kill us if they could, but are held at bay by our immune system. In fact, most pathogens get us exactly as sick as they want us to.

    I’ve got a post coming out tomorrow that flushes this concept out a bit, but you can find it at the old site here.

  7. #7 Scott
    November 4, 2010

    “In fact, most pathogens get us exactly as sick as they want us to”

    Eeeeep – I know its common place and I know I do it too, but this line struck me as really teleological. I’d prefer:

    “Pathogens make us as sick to a level that best suits them because they have been selected from ancestors that survived better by delivering a level of sickness that was to their advantage”

    Eeeeep – that sounds long winded. No wonder we cheat with teleological explanations.

  8. #8 Kevin
    November 4, 2010

    How about: “Pathogens have evolved to maximize replication AND transmission. To that end, making us really sick or dead is not necessarily beneficial.”

    The repost of that article I mentioned in 6 is now up

  9. #9 Scott
    November 5, 2010

    Yes this is better and avoids the teleological wording I was commenting on. I bring it up because I find while generally my thinking is not teleological, I still word scientific ideas in teleological language too often. This is probably, in part, to communicate with people who do not (most non-scientists) and sometimes I think its because I’m lazy. I’m on a mission to eliminate it from my writing and other peoples writing :).

    Every now and again I read a scientific paper which refers to evolutionary processes in a completely non-teleological way and when it is well written it is just awesome to read.

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