Inhibiting MRSA's ability to degrade RNA slows the spread of the bacteria

Scientists have demonstrated that stopping the ability of methicillin-resistant Staphylcoccus aureus (MRSA) to degrade RNA can inhibit its spread, both in the laboratory and in infected mice. The team of researchers is led by Paul Dunman of the University of Rochester Medical Center and includes scientists from three other laboratories. These results are reported February 10 in the open access journal PLoS Pathogens. MRSA infections are extremely virulent. The superbug causes nearly 500,000 hospitalizations and 19,000 deaths in the United States each year. The bug can be acquired in the community or in hospitals. MRSA is able to adapt quickly to changing conditions by breaking down its RNA molecules and using component parts to build new RNA sequences.

Dunman's research focused on one molecule, RnpA, which they found to be involved in the RNA degradation process. Inhibiting degradation is believed to be an effective means of slowing MRSA. This may be because, in the absence of recombination, the bacteria could be overcome by an array of confusing instructions that should have been turned off or because there will no longer be a supply of raw materials with which to build essential new RNA molecules.

The team isolated one molecule RNPA1000 that inhibited growth of the most common strains of MRSA as well as other bacterial pathogens of healthcare concern. It is active against biofilm-associated bacteria, and did not impact the effectiveness of other drugs used against MRSA in laboratory tests. In tests on mice, RNPA1000 was moderately effective against MRSA – one half of mice treated with a large dose of the molecule survived, while all of the mice in the control group died.

RNPA1000 may be considered a prototype of a new class of antibiotics, but showed limited toxicity to human cells in large doses, which suggests that the molecule in its present form will not be suitable for treating MRSA in human populations. Dunman and his colleagues are now investigating creating safer, more potent alternatives.

Source: Public Library of Science