Wednesday, February 04, 2009

Bacteria can mobilize a fifth column

I recently had to deal with a bacterial upper respiratory infection. Something to ponder about such problems is that not only did the little nasty have to gain a foothold on my immune system, but it also had to elbow a lot of other bacteria out of the way. After all, my respiratory tract is open to the air and is far from sterile; there is a whole ecosystem of bugs which generally get along with me. For an infection to take hold, either one of the regular residents has to go bad or the newcomers must steal some space.

A recent abstract in PNAS (alas, not an open access paper) provides a fascinating window on how that elbowing takes place. Staphylococcus aureus (aka the home front) is a standard resident of the respiratory tract (which, of course, can be nasty on its own if it gets through the skin) which Streptococcus pneumoniae (charming moniker! aka the invaders) must push aside. It turns out that one weapon the invaders use is hydrogen peroxide (H2O2), a staple of many home medicine cabinets -- though not mine growing up; Dad still favors tincture of iodine (curiously, cuts & scrapes often went unreported!).

Okay, that seems straightforward. Well, except the question of why the invaders themselves don't suffer some blowback. But it actually gets more interesting, because it turns out the H2O2 dose is sub-lethal. Huh? The invaders come in with flame throwers but set them to warm & cozy?

But sub-lethal doesn't mean physiologically irrelevant. The dose is enough for the home front to worry, as H2O2 can cause all sorts of damage. Indeed, the dose is strong enough to set off the SOS system, a DNA damage response.

The SOS system has an interesting side angle. Many bacteria carry dormant viruses, better known as lysogenic phage, within their genome. These viral genomes are integrated within their hosts' DNA and generally keep quiet, getting a free replication ride every time their host divides. However, that free ride isn't much good if your host dies with you in it, so these phage listen to the SOS response -- and when they hear it they go into their lytic phase, pumping out lots of virus and generally killing their host on the way out.

So now we have a picture: spook the home front enough that a fifth column of phage rises within and destroys them. Nifty.

Except, we're back to the blowback problem -- unless the invaders are also free of lysogenic phage they're going to have the same problem. However, it turns out that H2O2 does not activate the SOS response in the invaders, because they apparently are resistant to H2O2's DNA-damaging effects.

Understanding that resistance is a next area for work. Potentially, disabling it would offer an interesting antibiotic angle -- an antibiotic that was specific for the invaders by letting them blow themselves up. That's a big stretch (and the economics of antibiotic development are horrendous -- hence very few companies try it or stay in it) so don't hold your breath (or cough) waiting for it -- but it is a fun aspect to ponder.

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