Staphylococcus aureus is a difficult bug to kill. The bacterium is responsible for more American deaths each year as HIV / AIDS, partly because it is rapidly developing resistance to antibiotics. Scientists have struggled to understand how it ticks, but the researchers believe they may have found a way to conquer S. aureus by blocking its ability to perform a critical task :. recycling
Recycling is so important that even bacteria do. They cut the RNA plans necessary for protein design and assemble them in new directions. Researchers have known for over 20 years how the so-called gram-negative bacteria such as Escherichia coli degrade and recycle their RNA. But the process for gram-positive bacteria such as S. aureus is remained uncertain.
In the new study, researchers led by Paul Dunman, an infectious disease specialist at the University of Rochester in New York, the identified genes that were more active when S. aureus recycled quickly RNA. Blocking the activity of a protein known as the RNPA arrested recycling, indicating that the team Dunman had found a key enzyme.
The discovery of EPS is important Dunman said, because it provides a new target for antibiotic development. If bacteria could not recycle its RNA, two major problems arise. First, Dunman said, the bug would waste energy by following the instructions obsolete and turning RNA into proteins, there is no need. More importantly, it would run out of raw material with which print instructions, grinding everything in the cell to a sudden stop. "If you can stop the enzymes involved in this process with a small molecule or chemical," says Dunman, "this chemical may be an antibiotic."
To this end, the team screened nearly 30,000 small molecules to identify compounds that inhibit the action of RNPA. the researchers found that 14 did the trick, but a molecule called RNPA1000-was particularly effective against S. aureus . RNPA1000 killed cells all 12 main strains of methicillin-resistant S. aureus (MRSA), a major scourge of hospitals in the United States and elsewhere. It is also effective against strains resistant to antibiotics, gram-positive Streptococcus pneumoniae S. pyogenes and Enterococcus faecium , which cause diseases of meningitis to cardiac infections.
the team showed RNPA1000 that can stimulate the activity of antibiotics already on the market, but they do not yet know how. The chemical also kills S. aureus biofilms, which are a frequent cause of infection of the implanted catheters and other medical devices and are notoriously resistant to the action of antibiotics.
The drug worked in mice, too. Half of S. aureus mice infected recovered from their infections when treated with RNPA1000, while none of the untreated mice did, the team announced today online PLoS Pathogens .
RNPA1000 showed some toxicity when applied at high doses in human cells, so that the group seeks Dunman compounds closely related to RNPA1000 that can still prevent RNPA but without the side effects toxic.
Moreover, said Dunman, bacteria will eventually develop resistance against antibiotics, no matter how methodically selected. RNPA1000 is no exception, he said, "but the frequency [of resistance] in a laboratory environment is extremely, extremely low." This means that the bacteria must RNPA1000 resistance develop slower than other antibiotics.
Robert Daum, director of MRSA Research Center at the University of Chicago in Illinois, called the "creative" study and said it offers a new way to target the epidemic of MRSA. "What is important about this for me is not necessarily that work very could be the answer to the problem," he said, "but we look at how this bug does its dirty work in patients and how can we prevent this . "
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