Thursday, August 20, 2009

Qnr, A candy coated pill?

Fluoroquinolones are rapidly becoming the most heavily consumed antibiotics in America. This trend started in 2001 after the anthrax attacks because ciprofloxacin was the only antibiotic approved for treating anthrax. Prior to time, beta-lactams (penicillin and other similar antibiotics) had been the most popular because of their low toxicity and activity against a broad spectrum of microbes. However, the patent life on most beta-lactams was running out so marketing of them was decreasing. The timing of the anthrax attacks and the waning hype for beta-lactams created the perfect opportunity for fluoroquinolones to move to the forefront of prescription formularies.

Fluoroquinolones kill bacteria by inhibiting the exzyme known as DNA topoisomerase. That enzyme releases supercoiling tension as the double helix is unwound during DNA replication. If that enzyme is knocked out, the DNA gets tangled up and breaks and the cells die. Bacteria have a few ways of protecting themselves from fluoroquinolones. Their cell walls can mutate so that they become less permeable to the antibiotic. They can express efflux pumps that export the antibiotic from inside them. They can also express the gene qnr. The Qnr protein, encoded by that gene binds to DNA topoisomerase and prevents fluoroquinolones from doing so. However, the topoisomerase can still perform its regular role of relaxing supercoiling tension so the cells don't die.

I have been doing some work on qnr and it turns out that there are some tricks in manipulating the DNA encoding a gene that is involved in the manipulation of DNA. I sometimes wish that genes were large enough that I could throw them on the floor and stomp on them when they start playing tricks on me the way that this one does. I sometimes also wish that I could purify enough DNA so that I could taste it. In High school, my biology teacher told us that DNA is candy-coated (referring to the deoxyribose sugars that make up its backbone). I often wonder if it is really sweet. Some days, I very much doubt it. It might be easier to have an agreeable relationship with qnr if I knew there was some positive aspect to it.

The picture below is a portrait of me working on qnr. (I'm not the hand)

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