Monday, October 23, 2006

Monday Micro: Strep on Steroids

This weeks paper covers Streptococcus—the bacteria that gives little kids alllll over the world strep throat every winter. It likes to invade your tonsil cells, or sometimes cuts and wounds. They like epithelial cells. Well bacterial infections in your flesh are never a good thing, but in the mid 1980’s, something strange happened. No, not just the rise of fundamentalist Christianity in the US, strep infections were killing people, through a different kind of toxic shock syndrome, and through necrotic fasciitis. Do NOT Google necrotic fasciitis after you eat. Or before you want to eat. Seriously.

So what happened? A sweet, sweet lesson in evolution. Strep stole a gene from a phage (yes, a bacteria stole a gene from a virus), and it learned a new trick:

Emergence of a bacterial clone with enhanced virulence by acquisition of a phage encoding a secreted phospholipase A2

M3 strep infections have a higher death rate than other strains of strep. So these guys compared genomes of strep collected over the past 60 years, trying to find out what was so different, so deadly about M3. They found that M3 had stolen a phospholipase A2 gene from a phage virus (arch enemy of the bacteria) called SlaA. SlaA is the same stuff that you find in Australian brown snake venom. Yeah. They aren’t connected, but its still cool. Hehehe!

So these guys wanted to be sure they found the ‘right’ different gene in M3. So they went through a series of simple experiments to answer some basic questions:
1—What does SlaA do if you put it on tonsil cells?
Okay, easy enough to answer! Put some purified SlaA proteins on a culture dish of cells, watch what happens!
….. Nothing happened.

2—Okay… So what happens to the bacteria if you take away its SlaA gene?
They took away the M3s SlaA gene by making a delta-SlaA mutant and threw it on some cells! The bacteria behaved ‘normally’—they infected the cells, but not crazy nuts killing everything like the wild-type M3. So they were on to something! More experiments!
2A—Take a wt M3, but add SlaA antibodies to block it from doing anything. The ‘wt’ M3 acted more like a delta-SlaA mutant (missing SlaA)!
2B—Take a delta-SlaA mutant, and add exogenous SlaA to see if you can restore its phenotype. Sure enough, mutants complemented with SlaA proteins started killing more cells!

3—Well what the hell is going on??
When M3 strep hits saliva or tonsil cells, it starts secreting SlaA and gets it into the cells (remember, exogenous SlaA on its own didn’t do anything, it must act within the cells). SlaA works inside the cell to increase M3s ability to adhere to cells, and it itself toxic. They still need to work out the details (how, exactly, does SlaA get in? what does it do when it gets there?), but they’ve got a good case that in one fell swoop, this strain of bacteria stole a gene from a virus and became more virulent. This isn’t the *first* time this has happened (look at your own genome!) and evidently has had a huge impact on the evolution of life on this planet.

No comments: