The most common cause of death among people diagnosed with cystic fibrosis is chronic lung infections, which in some cases, are becoming even more difficult to treat.
The bad bacteria that cause lung infections have evolved to become resistant to a wide range of the antibiotics once used to kill them. In particular, physicians have relied on the class of potent antibiotics known as polymyxins as their last line of defense when the bacteria do not respond to more typical antibiotic treatments. But now, some bacteria have developed resistance to even those drugs.
Greenberg’s research focuses on developing treatments that can make polymyxins effective again. Polymyxins—which mimic a component of the body’s own immune system called cyclic antimicrobial peptides—are able to root out the bad bacteria by detecting the negative charge that surrounds their cell membranes.
“Polymyxins are able to identify and kill the bacteria,” Greenberg said. “But these bacteria have developed a pathway made up of a set of several proteins that can actually change the charge around the cell membrane. It actually disguises these bugs to resemble human membranes.”
Greenberg is working on developing drug compounds that can target the proteins responsible for flipping the genetic switch that causes the charge to change, allowing polymyxins, as well as the body’s native cyclic antimicrobial peptides, to once again recognize the bacteria.
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