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Scientists have discovered a new way to attack dangerous pathogens, marking a hopeful next step in the ever-escalating battle between man and
microbe.
In a paper published online Feb. 10 in the journal PLoS Pathogens, scientists demonstrate that by stopping bacteria's ability to degrade RNA – a "housekeeping" process crucial to their ability to thrive – scientists were able to stop methicillin-resistant Staphylococcus aureus or MRSA both in the laboratory and in infected
mice.
The team, headed by a microbiologist at the University of Rochester Medical Center, is now developing closely related compounds designed to be much more potent than the one discussed in the
paper.
"This offers a whole new way to go on the offensive against some of the world's most dangerous bugs," said the leader of the group, Paul Dunman, Ph.D., associate professor of Microbiology and Immunology at the University of Rochester Medical Center and formerly of the University of Nebraska. "We're hoping our research opens the door to an entirely new class of
antibiotics."
The team also includes scientists from the University of Nebraska, the University of Arkansas, Vanderbilt University, and the University of North Texas Health Science Center.
Dunman's team discovered that a molecule known as RnpA is central to the degradation process. After nailing down the activity of RnpA, the team tested more than 29,000 compounds in its search for one that inhibits its activity. The team found one, a small molecule called RNPA1000, that brings MRSA nearly to a
standstill.
The team found that RNPA1000 is active against the predominant MRSA types circulating in the United States, vancomycin intermediate susceptible S. aureus (VISA) and vancomycin-resistant S. aureus (VRSA). The compound also showed significant antimicrobial activity against a host of other bugs tested, including Staphylococcus epidermidis, antibiotic-resistant Streptococcus pneumoniae, Streptococcus pyogenes, and vancomycin-resistant Enterococcus faecium.
The agent does not affect other drugs used to treat MRSA infections, including vancomycin, daptomycin, or rifampicin; it does affect oxacillin, making it more potent. That find might make it possible to eventually combine an agent like RNPA1000 with other drugs that also target the
infection.
In addition to Dunman and Olson, other authors of the paper include post-doctoral associate Christelle Roux of the University of Rochester; Lisa Kuechenmeister, Kelsi Anderson, Tami Lewis, Oluwatoyin Asojo, and Khalid Sayood of the University of Nebraska; graduate student John Morrison of the University of Nebraska Medical Center, currently a visiting scientist in Dunman's Rochester laboratory; Sonja Daily, Karen Beenken, and Mark Smeltzer of the University of Arkansas; Michelle Reniere and Eric Skaar of Vanderbilt University; and William Weiss, Mark Pulse, Phung Nguyen, and Jerry Simecka of the University of North Texas Health Science Center.
These researchers are among scientists at two dozen laboratories around the world with which Dunman works. He is also a founder and owner of Caddis Research LLC, which is developing antimicrobial agents that target bacteria that pose a threat to public health, and he is a consultant for Pfizer Research.
The project was funded by the National Institute of Allergy and Infectious Diseases, the American Heart Assn., and the Nebraska Research
Initiative.
Source
University of Rochester Medical Center
(MDN)
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