Burkholderia Beware

Nanoemulsions target infection deadly to cystic fibrosis patients

Even though it’s a common bacterium found in soil and water, most people have never heard of Burkholderia cepacia. These hardy microbes are usually harmless, unless you have cystic fibrosis or a lung condition called chronic granulomatosis disease (CMD). For people with these diseases, Burkholderia infection is a death sentence.

“Every CF patient knows about Burkholderia and it strikes fear in their hearts,” says John LiPuma, M.D., professor of pediatrics and communicable diseases. “It’s highly resistant to all antibiotics, and essentially incurable.”

Scientists don’t know why these bacteria are lethal to people with cystic fibrosis, but with more CF patients living into adulthood, LiPuma says it’s a growing problem. About 10 percent of adults over age 18 with cystic fibrosis are infected, he says. Even if they avoid Burkholderia, CF patients remain vulnerable to other drug-resistant bacterial killers.

LiPuma has been collecting and studying antibiotic-resistant bacteria since the mid-1980s. He says he’s been contacted many times over the years by people who believe they’ve found something new to kill Burkholderia. Nothing ever has worked.

So it was with some degree of skepticism that LiPuma met with James Baker, M.D., the Ruth Dow Doan Professor of Biologic Nanotechnology, to discuss testing a nanoemulsion called NB-401 against Burkholderia and other drug-resistant bacterial pathogens that infect CF patients.

The collaboration between Baker and LiPuma was encouraged by Carroll Haas, president of the Carroll J. Haas Foundation. The foundation, which has supported LiPuma’s research for many years, provided funding that allowed the promising new research to begin.

Nanoemulsions are made from ultra-small droplets of soybean oil and agents that affect surface tension suspended in water. Baker developed the technology and founded an Ann Arbor company called NanoBio Corporation to develop and market it.

“Nano-sized particles interact with bacterial cell membranes in ways that disintegrate and kill the cell,” explains Joyce Sutcliffe, Ph.D., NanoBio’s vice president for research.

LiPuma admits he stacked the deck against NB-401. He searched his repository of 20,000 specimens for the “most drug-resistant bacteria I could find.” LiPuma selected 75 strains of Burkholderia and 75 strains of other bacteria found in people with cystic fibrosis. He put the bacteria into test tubes with various concentrations of the nanoemulsion and waited to see what happened.

Much to LiPuma’s surprise, “It killed everything,” he says. “We could dilute it 16-fold and still get very good killing.”

To make it more of a challenge, LiPuma then tested NB-401 on bacteria in sputum from CF patients, which can neutralize many antibiotics, and on bacteria growing in biofilms. Biofilms are collections of microorganisms that attach to a solid surface and form a protective envelope around the bacteria inside, making them especially resistant to the effects of antibiotics. While it required stronger concentrations of the nanoemulsion to kill the bacteria, “NB-401 passed every test,” LiPuma says.

Currently, LiPuma is testing NB-401’s bacteria-killing effects in mice infected with Burkholderia. He wants to test the nanoemulsion’s bug-killing ability when it’s aerosolized with saline solution and inhaled into the lungs. If drugs for CF infections can be targeted directly to the site of infection, it may be possible to give higher doses without the side effects and complications caused by high doses of antibiotics given systemically.

Based on the encouraging results from LiPuma’s initial tests of NB-401, NanoBio Corporation is convening an advisory panel of cystic fibrosis experts to evaluate the preliminary data and recommend how the company should proceed. Taking a new drug through the pre-clinical and clinical testing required by the U.S. Food and Drug Administration is expensive and risky. It’s a high-stakes decision for any business, especially a small company like NanoBio, but clinical studies are the only way to know if a new treatment will work.

“Potentially, this could be an important advance for the treatment of cystic fibrosis, but we need to test it in people to know for sure,” says Baker. —Sally Pobojewski

More information on nanoemulsions

HPV Strikes Again

Head and neck cancer used to be most common in older people who drank alcohol, smoked or chewed tobacco. But now physicians are encountering what Thomas Carey, Ph.D., professor of otorhinolaryngology, calls an epidemic of oral head and neck cancers in younger men and women. These tumors of the tonsils and base of the tongue often develop in patients who don’t smoke. They are caused by the sexually transmitted human papillomavirus (HPV) which also causes cervical cancer.

“Our biggest challenge is determining how best to treat patients with tumors that stem from tobacco and alcohol use, as opposed to tumors linked to HPV,” says Frank Worden, M.D., an assistant professor of internal medicine. “We now know they are two different cancers.”

A one-size-fits-all approach to treating cancer doesn’t work. Every patient’s cancer is unique, and survival depends on choosing the most effective therapy for each cancer. This is especially true for cancer of the mouth, tongue and tonsils. These malignant tumors all look alike, but some are much more dangerous than others.

So how are doctors supposed to know what to do? The answer, according to Carey, Worden and other researchers at the Comprehensive Cancer Center, is in the tumor’s biomarkers. In recent research, these scientists found that patients whose advanced head and neck tumors contained specific molecular markers responded well to chemotherapy and radiation. Patients whose tumors had different biomarkers did not respond to conservative treatment. They required more aggressive chemotherapy, in addition to surgery.

One bit of good news from their research, according to Carey, is that HPV-positive tumors usually responded to conservative chemotherapy and radiation. Patients whose tumors contained high levels of the epidermal growth factor receptor called EGFR in combination with other markers were much less likely to survive even after surgery and aggressive treatment.

Says Carey, “The high incidence of HPV-associated cancers also suggests that all adolescents, not just young women, should be vaccinated against this cancer-causing virus.” —SP

An expanded version of the story
Patient information on head and neck cancer