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multi-drug resistance

Red blood cell infected with malaria-causing parasites

Caption: Colorized scanning electron micrograph of a blood cell infected with malaria parasites (blue with dots) surrounded by uninfected cells (red).
Credit: National Institute of Allergy and Infectious Diseases, NIH

As a volunteer physician in a small hospital in Nigeria 30 years ago, I was bitten by lots of mosquitoes and soon came down with headache, chills, fever, and muscle aches. It was malaria. Fortunately, the drug available to me then was effective, but I was pretty sick for a few days. Since that time, malarial drug resistance has become steadily more widespread. In fact, the treatment that cured me would be of little use today. Combination drug therapies including artemisinin have been introduced to take the place of the older drugs [1], but experts are concerned the mosquito-borne parasites that cause malaria are showing signs of drug resistance again.

So, researchers have been searching the genome of Plasmodium falciparum, the most-lethal species of the malaria parasite, for potentially better targets for drug or vaccine development. You wouldn’t think such work would be too tough because the genome of P. falciparum was sequenced more than 15 years ago [2]. Yet it’s proven to be a major challenge because the genetic blueprint of this protozoan parasite has an unusual bias towards two nucleotides (adenine and thymine), which makes it difficult to use standard research tools to study the functions of its genes.

Now, using a creative new spin on an old technique, an NIH-funded research team has solved this difficult problem and, for the first time, completely characterized the genes in the P. falciparum genome [3]. Their work identified 2,680 genes essential to P. falciparum’s growth and survival in red blood cells, where it does the most damage in humans. This gene list will serve as an important guide in the years ahead as researchers seek to identify the equivalent of a malarial Achilles heel, and use that to develop new and better ways to fight this deadly tropical disease.

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Dirt

Caption: Researchers found a new class of antibiotics in a collection of about 2,000 soil samples.
Credit: Sean Brady, The Rockefeller University, New York City

Many of us think of soil as lifeless dirt. But, in fact, soil is teeming with a rich array of life: microbial life. And some of those tiny, dirt-dwelling microorganisms—bacteria that produce antibiotic compounds that are highly toxic to other bacteria—may provide us with valuable leads for developing the new drugs we so urgently need to fight antibiotic-resistant infections.

Recently, NIH-funded researchers discovered a new class of antibiotics, called malacidins, by analyzing the DNA of the bacteria living in more than 2,000 soil samples, including many sent by citizen scientists living all across the United States [1]. While more work is needed before malacidins can be tried in humans, the compounds successfully killed several types of multidrug-resistant bacteria in laboratory tests. Most impressive was the ability of malacadins to wipe out methicillin-resistant Staphylococcus aureus (MRSA) skin infections in rats. Often referred to as a “super bug,” MRSA threatens the lives of tens of thousands of Americans each year [2].

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