To test the technique, the authors embedded cells of the opportunistic pathogen C. albicans in each of the 1,200 tiny dots of alginate on the surface of the microarray. Under the microscope, these nano-biofilms of C. albicans, each of which was only 30 nanoliters, exhibited the same growth habits and other outward characteristics as conventional, macroscopic biofilms, and achieved maximum metabolic activity within 12 hours. The tiny cultures were then treated with a wide range of candidate drugs from the National Cancer Institute library, or with different FDA-approved, off-patent antifungal drugs in combination with FK506, an immunosuppressant, for identifying individual or synergistic combinations of compounds effective against biofilm infections. Co-author Anand Ramasubramanian of the University of Texas at San Antonio says that the tests prove the utility of the technology in screening combinations of drugs.
"The antifungal screening results were similar to results in larger macroscale techniques. That gives us confidence that it could be used as a tool to replace existing techniques," says Ramasubramanian.
Going forward, Ramasubramanian says he and his colleagues are testing the microarrays with polymicrobial cultures - mixtures of fungi and bacteria - to see whether the technology can be used to explore treatments for mixed infections. They are also exploring clinical applications for the technique, testing patient samples against an array of drugs or combinations of drugs to develop tailored therapies.
Lopez-Ribot says their microarray technique is just the latest development in a decades-long trend toward the tiny in science. "Things are moving toward smaller scale, more powerful techniques. You don't need millions of cells for these assays like we used to - maybe a few cells will do."
|Contact: Jim Sliwa|
American Society for Microbiology