Pulse Magazine Fall 2019

Page 18



he says. He hopes to see pharmaceutical companies play a bigger role. “The process of drug development is expensive,” he points out. “Yet a patient typically uses an antibiotic once for a couple of weeks and then it’s done, if all goes well. There’s not enough profit margin for pharmaceutical companies. So we need to incentivize more collaborations between pharma and academia. “I’m on the other side, as a very basic scientist trying to understand how proteins work. But I also recognize that antibiotic-resistance is a fundamental problem that we’re facing. So I’m working to see if we can develop drugs to reverse that.”

By Am an da Ca st le ma n


the U.S., at least 2 million people succumb to infections that have mutated to defy all medications—and 23,000 of those cases are fatal each year, according to the Centers for Disease Control and Prevention. It considers antibiotic resistance one of the biggest health challenges of our time. Vasileios Petrou, PhD, assistant professor and Chancellor Scholar, is in the vanguard of the fight at NJMS. The work he is doing may help resolve antibiotic resistance, a threat that some experts warn could wipe out humanity. “The situation is becoming worse, and could reverse many medical advances of the last 70 years,” he says. “This is something that needs to be addressed now with accelerated, incentivized development of new antibiotics, as well as ways to make our current drugs relevant again.”

Petrou, who joined the Department of Microbiology, Biochemistry and Molecular Genetics and the Center for Immunity and Inflammation in July 2019, is exploring how to disrupt antibiotic resistance on a molecular level, by targeting proteins in the cell membranes of attacking bacteria. He’s made significant strides, chronicled in a 2016 report for the journal Science. He and his colleagues solved the atomic structure of the enzyme ArnT that changes the electrostatic charge of the

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bacterial membrane, making bacteria more resistant to polymyxins—“lastresort drugs” often called into play for infections that don’t respond to other antibiotics. The mechanism is simple, he explains: The enzyme ArnT reduces the charge of the outer surface in bacteria like E. coli and Salmonella, preventing them from bonding to the antibiotic, so the drugs cannot do their job. “Think about it like glue,” he explains. “The bacteria are diluting the glue so the antibiotic doesn’t stick as well to them.” This work helped him win a highly competitive National Institutes of Health grant in 2017 and he is carrying the research forward in his new NJMS lab. He is currently working with senior research scientist Apostolia Baki, PhD, and hopes to add two postdocs shortly. “We’ve had some initial success and we now have a much better understanding of how the enzyme works than we had three years ago,” he says. “The same mechanism is at play across different species of bacteria, which gives us more confidence that we’re targeting the right thing.” Originally from Greece, Petrou earned a neuroscience PhD at New York’s Icahn School of Medicine at Mount Sinai before delving into structural biology, specifically studying proteins embedded in cell membranes. “I’ve had a very interesting scientific trajectory,” he notes.

“I’m happy I found my niche; that’s very important for a scientist.” He has been doing some preliminary drug development and has a patent pending with his former postdoctoral advisor at Columbia University Irving Medical Center. He emphasizes that solutions will take time. “Once we find a small molecule drug that can reverse resistance, we forward for FDA approval. In most cases the process would take about 10 years.” Efforts like this need to be paired with the development of new antibiotics,

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