Combating antibacterial resistant diseases with lasers

Since the mass introduction of antibiotics last century, bacteria have been fighting back with an arsenal of defensive mechanisms. Some produce enzymes that can digest the antibiotic molecule before it takes effect. Others have developed cell membranes that can recognize antibiotics and close down the openings by which they would normally enter. Some can even eject the antibiotic molecule after taking it into the cell.

These defenses are growing faster than researchers can create new antibiotics to avoid these problems.

“We are facing a war with bacteria,” said Dr. Vanderlei Bagnato, a professor of biomedical engineering at Texas A&M University. “Antibiotic-resistant pneumonia is already killing 4 million people a year. If we don’t do something about it now, people in the future are going to be dying of infections that today are easily treated with antibiotics. Then, we are not talking about 4 million people dying a year; we are possibly talking about hundreds of millions.”

Bagnato intends to fight back. His weapon of choice in this war is light. This essentially drug-free strategy allows him to avoid one of the most dangerous parts of the escalating arms race with bacteria: antibiotics themselves.

“You have to understand that an antibiotic is a poison,” Bagnato said. “It can kill your liver, your kidneys — it can kill everything in you. So, doctors want to use the absolute smallest amount. We call this the Minimum Inhibitory Concentration (MIC).”

The problem is that this MIC is constantly rising. As bacteria get better at avoiding the antibiotic molecules, doctors must administer increasing amounts of the drug to overwhelm the microbes’ defenses. Eventually, the amount of antibiotic required to kill the bacteria hits levels where it would also kill the patient.

At this point, the disease has become functionally untreatable. Light-based therapies can change that.

“Light can go places where instruments will not,” Bagnato said. “If I can find ways to make light penetrate you, I can reach cells and do things in there without cutting you or introducing a catheter. And I can use many different colors of light to activate and deactivate a wide variety of molecules.”

For Bagnato’s methods, light makes the second strike in a one-two punch. The first step of treatment is to administer a safe but photoreactive compound. The method varies depending on the location of the infection. For the treatment Bagnato already developed to combat antibacterial resistant throat infections in Brazil, patients merely need to hold a specially formulated lollipop in their mouths.

For a complex disease like antibacterial resistant pneumonia, patients will have to inhale a photoreactive substance carried in an aerosol.

When the infrared light that has passed harmlessly through the patient’s body comes into contact with the photoreactive substance they previously inhaled, the result is an instantaneous chemical reaction —   one that Bagnato has carefully planned using his decades of knowledge.

“I’m an atomic and molecular physicist. I use that knowledge of how light promotes reactions and how it interacts with atoms and molecules,” Bagnato said. “I can destroy the bacteria’s flux pump. I can open holes in the membrane. I can kill the mechanisms that the bacteria use to defend themselves.” 

With their defenses removed, the bacteria are vulnerable to a final coup de grace: the antibiotic that they had previously rendered useless.

“When those defenses are removed, safe levels of antibiotics can act again. What I’ve done with light has brought the MIC back down to the normal level,” Bagnato said. “Immediately after I kill the defense mechanisms, I administer the antibiotic, and the antibiotic kills the bacteria.”

The war against antibiotic resistant disease is only one of many that Bagnato is currently waging. His research runs the entire spectrum of pressing medical issues, from antibiotic resistant diseases to cancer and diabetes — all problems that are only going to become more threatening in time. Over his career as a physicist turned biomedical engineer, Bagnato has founded over 40 companies, become a member of the Vatican’s Pontifical Academy of Sciences, been inducted into the U.S. National Academy of Sciences and the National Academy of Engineering.

At age 67, he has no intention of giving up the fight.

“Each generation has to carry the next without asking for anything,” Bagnato said. “It is scary. I’m afraid for my grandkids, who are going to face a different world. But I still get thrilled with each new discovery. People say that Murphy’s Law means everything that can go wrong will go wrong, but that doesn’t work for me. Go be wrong. I have crazy ideas, but I still go and try them. It doesn’t always work in the way that I imagined, but it works somehow. Even the ones that had everything fail work in some way. So, Murphy is my friend.”

50 years from now, millions of patients may owe their lives to Bagnato’s work — with a little help from Murphy’s Law.