Halted RNA degradation

MRSA, which stands for Methicillin Resistant Staphylococcus aureus, is nearly impossible to defeat once an infection settles into the body but researchers may have found a new weapon.  Details of the research are reported online in the journal PLoS Pathogens.

One of the reasons MRSA is so difficult to treat is that the bacteria live inside the extracellular matrix of a biofilm.  This biofilm is prevents many types of antibiotic from passing throug to get to the bacteria underneath.  A new drug can actually pass and deliver a significant puch to the microbes.  

"MRSA infections are among the most virulent infections known and can be acquired in the community or in hospitals. They cause nearly 500,000 hospitalizations and 19,000 deaths in the United States each year—more deaths than are caused by AIDS." ^[1]

These bacteria are able to produce so many variations, some of which confer antibiotic resistance, that are then selected for survival as environmental changes occur with the exposure to such antibiotics.  Making new RNA molecules from these DNA variations produces new proteins, such as enzymes that degrade antibiotics or new channel proteins that allow the antibiotics to be shipped out as fast as the drug enters, may help the bacteria to survive.  The DNA code is transcribed to produce RNA molecules that are translated to make new proteins.  When the RNA has done its task of translation, enzymes in the cell cytoplasm chew up the RNA molecules and recycle the RNA nucleotides for new transcription to occur.

New research is aiming at the  important cellular process, known as RNA degradation. Because bacteria reproduce so rapidly, the efficient turnover of RNA nucleotides is vital to their success.

“In less than three minutes, a new RNA transcript is made, the protein is made, and then the RNA is degraded, and that material is made available to make other RNA molecules.” (Rickey, 2011)

A molecule known as RnpA is one key in the degradation process. So researchers looked for substances that could inhibit the action of the degradation.  Nearly 30000 compounds were systematically tested in vitro for activity against the RnpA molecule.  Eventually one molecule was found- RNPA1000.  This molecule blocks the RnpA so that RNA is not degraded to nucleotides, causing the cells to continue making unneeded proteins and prevent the cells from making new proteins they do need.  They are basically starved of RNA nucleotides to continue their cell processes.

RNPA1000 has been shown to be effective against many types of MRSA spreading through the USA.  Other bacterial stains resistant to vancomycin and other antibiotics seem to be attacked by this new compound.  What is interesting to note is the activity against MRSA biofilms which prevent many antibiotics from reaching the bacteria.

“This is a great starting point,” says Dunman, the researcher who discovered the RNPA1000. “We’ve identified a compound that is very active against RnpA, and now we can use chemistry to try to increase its potency by hundreds of times, as well as make it less toxic to human cells. We’ve gotten a lead from the drug screen, and now we’re building a better molecule.” (Rickey, 2011)

So the race is on again!  Which species will create the better defence- humans searching for drugs that stop these bacteria or the bacteria creating new variations by mutations to escape the antibiotics?  Natural selection will always win out, it is just a question who is the winner!