Carolyn Cannon, M.D., Ph.D., pediatric pulmonologist and associate professor at the Texas A&M College of Medicine

Wielding Nature’s Sword: Researchers at Texas A&M discover new treatments against drug-resistant infections

December 11, 2014

Since World War II, antibiotics have saved countless lives by killing disease-causing bacteria. To this day, traditional antibiotics remain the only treatment against such illnesses, but overuse and misuse have caused some bacteria to develop resistance to commonly used antibiotics. These bacteria, known as multi-drug resistant organisms (MDROs), are able to survive and even multiply in the presence of antibiotics, making treatment against them nearly impossible.

But now, after decades of using the same basic ingredients for antibiotics, a new way to treat bacterial infection is finally on the horizon. Carolyn Cannon, M.D., Ph.D., and her team at Texas A&M Health Science Center have discovered that a new set of compounds synthesized by medicinal chemist Lászlo Kürti, Ph.D., with the University of Texas Southwestern Medical Center in Dallas, have the potential to kill MDROs. Specifically, the researchers have their sights set on methicillin-resistant Staphylococcus aureus (MRSA) – a bacterial infection caused by a strain of staph bacteria that’s become resistant to commonly used antibiotics, making it so hard to treat, it’s been deemed a “super bug.” This discovery is predicted to yield an entirely new class of treatments for a multitude of drug resistant infections.

“Microorganisms have been battling each other for millennia, so they have a whole armamentarium of ways to kill each other,” said Cannon, who is a pediatric pulmonologist and associate professor at the Texas A&M College of Medicine. “It’s just a matter of us noticing and isolating those weapons and then synthesizing them for use as treatments against pathogens, the bad guys.”

Penicillin and cephalosporin – the bases for the most commonly used modern antibiotics – were first isolated from fungi. Most new FDA-approved antibiotics are simply tweaks of those original molecules. The first molecule of Cannon and Kürti’s new class of antimicrobials was originally isolated by researchers more than a decade ago from a bacterium that originates from the ocean. Then, only tiny amounts could be extracted from cultures of the bacteria with great effort. Fast forward to present day, and the current team now has developed a simple method to synthesize the molecule and tweak it.

“The beauty of the discovery is that these compounds can now be synthesized in one pot in 30 minutes. It’s a very scalable procedure that can easily yield large quantities,” Cannon said. “We have been able to take the new compounds into the lab to study their activity, and have found that they are more active against MRSA than the gold-standard treatment, vancomycin. Plus, we have found compounds with better activity than the compound made by the bacterium from the ocean.” These constitute a completely new class of antimicrobial molecules that don’t look like anything else currently used in medicine.

While modern-day antibiotics readily go into solutions that can be injected, inhaled or ingested, these new molecules are not water soluble. That factor may seem like a major barrier, but thanks to new nanoparticle technologies, what was once an obstacle has become a momentous opportunity that Cannon’s group, as part of a National Institute of Health’s Program of Excellence in Nanotechnology, has the expertise to seize.

Nanoparticles are simply particles that exist on the nanometer scale (anything up to 100 nanometers is considered a nanoparticle). As a comparison, most bacteria are on the micrometer scale, averaging about a micron or two long. Even the largest nanoparticle – one that is 100 nanometers – is merely a tenth of a micron. Because they are so small, these nanoparticles contain some very useful properties. For instance, they can be designed to slip through sticky mucus and penetrate into biofilms. They can be synthesized from polymers, large molecules composed of many repeated subunits, designed to be broken down in the body.

“Think of a microscopic baseball with a rubber center covered by yarn, then cowhide. Our otherwise insoluble antibiotic contained in the ‘rubber center’ is shielded by a water-loving hydrophilic surface, the ‘yarn,’ which renders the nanoparticle compatible with suspension in a solution. You can decorate the outside, the ‘cowhide,’ with molecules that specifically bind to the surface of bacteria to allow accumulation of the drug at the site of the infection. This nanoparticle delivery is much more targeted than traditional antibiotics,” Cannon said.

Targeting in this precise manner allows for a dramatic drop in the amount of medication that a patient needs in order to kill infection. Further, targeting may spare beneficial bacteria that are often killed secondarily by traditional delivery of antibiotics that are dispensed throughout the body. What’s more, targeting may allow for the use of more potent drugs, since the drugs would merely affect the site of infection and not the entire body.

The next step for Cannon’s team is to test nanoparticles containing the antimicrobial molecules in animal models, which, she says, is very close to happening.

This piece was originally published on October 20, 2014.

— Lindsey Hendrix

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