Why we will never defeat the microbes (repost)

[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.