Small Molecule Adjuvant Reverses MRSA Resistance to Antibiotics

Drug developers have improved the performance of a small molecule adjuvant that had been shown to decrease the antibody resistance that protects MRSA (methicillin-resistant Staphylococcus aureus) bacteria from treatment.

Investigators at North Carolina State University (Raleigh, USA) have been working with 2-aminoimidazoles for several years. This emerging class of small molecules possesses the ability to inhibit and disperse biofilms across bacterial order, class, and phylum. They had reported previously that the synergistic effect between a 2-aminoimidazole/triazole conjugate and antibiotics could resensitize multidrug-resistant strains of bacteria to the effects of conventional antibiotics.

In the current study, which was published in the October 9, 2012, online edition of the journal Angewandte Chemie, they described a method for improving the performance of 2-aminoimidazole compounds so that susceptibility of MRSA strains towards oxacillin was increased 512-fold.

“You measure antibiotic effectiveness by growing bacteria in the presence of an antibiotic,” said senior author Dr. Christian Melander, professor of chemistry at North Carolina State University. “The concentration you typically want to observe is about one microgram per milliliter or less of the antibiotic to halt bacterial growth. At that point, the bacterial strain is considered susceptible to and treatable by that antibiotic. If a higher concentration of antibiotic is required to halt bacterial growth, the bacterial strain in question is considered untreatable. Some of the MRSA strains we work with require 512 micrograms per milliliter of the antibiotic of choice to control growth – 500 times over the limit. Adding our compound brought the level down to one microgram per milliliter again.”

The precise mechanism of how the 2-aminoimidazole compound reverses MRSA drug resistance remains to be worked out. However, Dr. Melander speculated, “We believe that our compound renders the bacteria unable to recognize the antibiotic as a threat, essentially stopping the defensive process before it can begin.”

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