Drugs That Kill Bacteria Can Also Make Them Stronger

By Johnathan Nieves ‘11

A recent study showed that exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug under development by Radnor, PA-based PolyMedix, Inc. shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.

If you don’t take your prescription antibiotics as your doctor advises, then listen up. Just last week (February 12) a paper published in the journal Molecular Cell described how exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug currently under development by Radnor, PA-based PolyMedix, Inc., however, shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.

Drug resistance has been a growing health concern for decades now since the introduction of penicillin in the 1940s, the first available antibiotic of its kind. Drug resistance occurs because of bacteria’s natural ability to evolve through mutations it incurs as it reproduces. As it turns out, researchers have found that low antibiotic dosages are triggers for increasing the rate at which bacteria mutate, thus, increasing the likelihood of drug resistance.

“Like anything in nature, bacteria have ways to fight its opponents, and do so either by pumping antibiotics out of themselves through a process called efflux, or by rapidly mutating and changing the shape of the target of attack of the antibiotic drug. They can do this, even with large doses of antibiotics, it’s their innate way to try to survive,” explains Bozena Korczak, Vice President of Drug Development at PolyMedix Inc..”

“Upping the antibiotic dosage may be a viable solution but not the ultimate one,” adds Korczak. Driven by science conducted at the University of Pennsylvania, PolyMedix is investigating a new type of antibiotic drug that works by imitating the human immune system.

PolyMedix’s investigational antibiotic agent, called PMX-30063, is the first of its kind with a new approach to address the serious health implications of drug resistance by mimicking host defense protiens. Unlike most antibiotics, host defense proteins work fundamentally different. Rather than crossing the bacterial membrane to find a target like most antibiotics, they selectively target the cell membranes integrity by poking holes into it. This diminishes the bacteria’s ability to remain intact and the bacteria and its internal components become degraded (See video demonstration by clicking on the image above).

Polymedix purports that this unique mechanism of action makes drug resistance unlikely to develop. Korczak insists that “the best approach to preventing this phenomenon is by directly attacking the bacteria’s cell membrane, rendering them destroyed and dead in a way that there is little chance of resistance.”

To study the ability of bacteria to resist an antibiotic drug, a laboratory experimental method known as “serial passage” is used by intentionally trying to create bacterial drug resistance. Using this experiment, PolyMedix has shown that resistance did not appear to its compounds in contrast to traditional antibiotics.

So far, data from two Phase I clinical studies demonstrate that the compound is safe and well-tolerated. PolyMedix is on schedule to complete the third and final segment of the ongoing Phase 1 study with PMX-30063 early this year and commence Phase 2 studies later this year.

PolyMedix has received 9 grants and research contracts from the National Institutes of Health and branches of the military to help support the development of its antibiotic compounds.

To view the press release associated with this piece, please click here.

To learn more about PolyMedix, Inc., please visit www.polymedix.com.