The Conservative Cat

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December 21, 2007

NMPDR - The Really Bad Strain of Staphylococcus Aureus

I'm going to get into political philosophy before this article is over, but I have to lay some groundwork first. The groundwork relates to the problem of antibiotic resistance in disease and how we're fighting it. You might also want to read this article about why antibiotic resistance is a problem and why only a comprehensive solution can work. Nothing I'm about to explain is necessary in order to understand the comprehensive solution, but it will help you to understand the nature of the problem itself.

In Texas, they're having problems with a disease called methicillin-resistant staphylococcus aureus (MRSA), and it's one of the core diseases being studied by Bruce's research group. If you click here, you can see the latest work on isolating the genes that enable MRSA to fight antibiotics.

Penicillin, the father of all modern antibiotics, gets its power from its ability to bind to bacterial proteins called PBPs. PBPs are used by bacteria to build cell walls. A bacteria without functioning PBPs can't build enough cell wall material to reproduce, which is why penicillin works. Some time back, staph bacteria began developing a protein called beta lactamase that destroys the penicillin molecules before they can neutralize the PBPs. So, methicillin was introduced, and after that vancomycin. Now even vancomycin is failing.

The mechanism defeating antibiotics in MRSA is something completely different from the technique that stopped penicillin. Instead of creating a chemical to destroy new drugs, the staph has evolved a new kind of PBP that is immune to the binding effect of the antibiotics. This means we need a whole different approach.

A lot of independent work in different directions is being expended to find that approach. For example, we now know that the gold-colored pigment that gives staph aureus its name helps it to fight white blood cells. If we can suppress the pigment, the germ ceases to be dangerous. We also know that when staph aureus is inside the body it has a very different metabolism from the one it enjoys when it sits on the skin. If we can find a drug that keeps it from switching into virulence mode, it would cure the disease without creating pressure for the bacteria to evolve a defense.

Such research starts with DNA databases like NMPDR. These databases contain educated guesses by molecular biologists about which genes do what. The work then proceeds to wet labs, where they create mutant bacteria strains with and without the identified genes. Lab mice are infected with the original and mutant forms of the diseases. If turning off the gene cures the disease, drug companies can use computer models of the proteins produced by those genes to determine if one of their drugs will do the trick. If the models find a suitable drug, the drug company can begin trials to determine if the computer models are correct. It's a long process, but it's a vast improvement over the trial-and-error process that prevailed in the last century.

It's worth noting that this process is not the result of some great government initiative to address a medical crisis. The NMPDR started its life as a new way to analyze DNA sequences, and got its funding as part of a completely unrelated scheme to defend against biological weapons. The NMPDR itself careened into a whole new way of annotating DNA, which in turn enabled us to add six new strains of staph aureus to our database in less than a month. (Two years ago I was proud of the fact that Bruce's group could annotate one genome in less than six months.) In the meantime somebody realized this stuff had applications in analyzing meta-genomes (which used to be called environmental samples). I have no idea what's going to come out of that, but it has several people at the lab very excited.

Here's the moral of the story: while the comprehensive government solution is still getting organized, serendipity has given us a new set of tools to fight disease. This happened even though we have profit-seeking drug companies competing against each other while grant-seeking science groups scrabble after funding with no concern over the big picture. Competition is working. The big picture is going nowhere.

Remember this the next time you hear about the need for a comprehensive solution.

Respectfully submitted,

Ferdinand T. Cat

# At Fri 5:53 PM | Permalink | Trackback URI | Comments (5) | More NMPDR | Tags: antibiotics bacteria bioinformatics biology conservative DNA medicine methicillin NMPDR penicillin philosophy staphylococcus aureus

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Comments

Posted by: Rosemary at December 22, 2007 2:05 AM

Posted by: Michael at December 22, 2007 2:24 AM

Posted by: Ferdy at December 22, 2007 3:28 AM

Posted by: PTG at December 25, 2007 9:50 PM

Posted by: Sanitary at August 28, 2008 2:02 AM