NSU Researcher Battles Resilient Microscopic Menace

Associate Professor Robert Smith with graduate student Ariane Kalifa at the NSU’s Center for Collaborative research.

In cellular research, scientists often battle microscopic entities that are capable of catastrophic impacts. Take for instance antibiotic-resistant bacteria, which continue to cause fatal infections that were once treatable. It’s estimated upwards of 10 million people will die annually from these infections by the year 2050.

Associate Professor and Research Scientist Robert Smith, a Nova Southeastern University researcher in the NSU Cell Therapy Institute in the Dr. Kiran C. Patel College of Allopathic Medicine, has been studying this resilient menace since 2009. He characterizes his work to develop tougher antibiotics as “Sisyphean” – a task that can never be completed.

“The incidence of antibiotic-resistant bacteria is certainly on the rise as a whole,” he said. “It varies from region to region, but nowhere is it getting better.”

Antibiotic-resistant bacteria have become one of the centerpieces of Smith’s research mainly because of the dire implications people will face if they are not addressed.

“If we don’t do something, people are going to increasingly die from infections that killed people in the 1800s,” he said. “Even routine ear infections could become deadly.”

The infections patients can contract while in the hospital are already becoming a problem because of antibiotic-resistant bacteria, Smith said. He anticipates routine hospital stays are going to get increasingly riskier, especially for those who are immunocompromised.

Associate Professor Robert Smith with graduate student Trent Moulder

Among the immunocompromised are people with HIV who don’t take their medication, the elderly, transplant patients, infants, and people who take immunosuppressant medicine such as those with arthritis. And in some cases, those susceptible to infections don’t have a medical issue.

“I know about an entire hockey team that got MRSA (methicillin-resistant staphylococcus aureus) from their equipment and they had to incinerate all of the equipment,” Smith said.

Smith and his fellow researchers have discovered new ways in which bacteria can tolerate and resist antibiotics by changing their metabolism (or how much energy they use as a cell). One of the researchers Smith collaborates with is Allison J. Lopatkin, an Assistant Professor of chemical engineering at the University of Rochester in New York. They recently wrote a paper on the metabolic phenomenon.

“This is starting to lead to the discovery of novel drug targets, and our research is now partially headed in that direction,” Smith said.

Smith’s NSU team is composed of one post-doctorate student, two graduate students, three M.D. students, two Master of Biometrical Sciences students, six undergraduates, and one research associate.

Smith uses a computer model that helps guide him toward the most promising direction to focus his research. He then tries to find drug targets for a very specific form of antibiotic called the “inoculum effect,” meaning the more bacteria you have, the more antibiotic you have to give that bacteria to beat it, keeping in mind there is a limit to how much antibiotic you can give someone.

Finding drug targets is a short-term approach, Smith cautions, emphasizing that figuring out a new way to kill bacteria that are less prone to resistance will be the key to curing infections, saving lives, and improving health in the future. It will take time, commitment, and money, he adds.

One example of an antibiotic-resistant bacteria is MRSA, which is responsible for several infections that are difficult to treat. MRSA is spread by contact – touching another person who has it on their skin or touching something that has the bacteria on it. MRSA is manifested as painful, swollen bumps that may look like pimples or spider bites. The bumps can become boils that may require surgical draining.

“When I was in school, MRSA was the big scary thing,” Smith said. “It’s still terrifying but we have other drugs that can treat it now. One of them is vancomycin. But now we’re starting to see strains of MRSA become resistant to antibiotics, our last line of defense. We’re dealing with this arms race, where we make a new drug, the bacteria figure out how to beat it and the process repeats itself.”

Antibiotic-resistant bacteria are a very old problem, Smith said, adding they were not only recognized by Scottish researcher Sir Alexander Fleming a few months after his discovery of penicillin in 1928, but have been pulled from bacteria dormant in permafrost in the Arctic that is 1,000-plus years old.

There are a few key reasons antibiotic-resistant bacteria have continued to thrive, Smith says. One is overuse of antibiotics.

“We use large amounts of antibiotics in the livestock industry as a protectant, but it also increases the size of some animals,” he said. “The animals basically pee it all out and it gets into the environment where it drives antibiotic resistance.”

Another reason is misuse of antibiotics.

“While doctors are certainly getting better at prescribing antibiotics, there are still some who will prescribe for things that antibiotics won’t work with, such as viral infections,” Smith said.

As Smith continues his battle behind the microscope, he says one of his triumphs has been the success of his students, who have gotten jobs at Duke University, the University of North Carolina, the University of Miami, Yale University, the University of Colorado, and others.

“I think the success that I enjoy the most is where my students have gone after leaving the lab,” he said. “They have landed some really good gigs.”

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