By Doug Bennett
In the medical and military fields, antibiotic-resistant bacteria can be formidable foes. Now, University of Florida Health researchers and their collaborators have a $75 million grant to identify a new, unique antibiotic that will protect public health.
Funding from the federal Defense Threat Reduction Agency will be used to study 28 compounds, eventually narrowing them down to one drug and a backup candidate that can destroy bacterial pathogens that would otherwise evade current antibiotics. The benefits should be twofold: Creating a compound that could be used to address a bioterrorism event while also treating stubborn infections among the public or hospitalized patients.
“We’re working to identify new and distinct therapeutics to treat diseases in general and address certain subclasses or organisms that could be misused,” said Henry Heine, Ph.D., an associate professor at UF’s Institute for Therapeutic Innovation in Orlando, part of the UF College of Medicine.
Heine and his UF collaborators will work with scientists at Curza, a biotechnology company in Salt Lake City that is developing the antibiotic. The UF Health scientists’ and physicians’ main roles will be analyzing the selected compounds’ effectiveness against various bacterial pathogens in preclinical models. That should ultimately lead to advanced therapeutic testing and human clinical trials, the researchers said.
Researchers say there is an urgent need to develop a novel antibiotic that can be used against high-consequence bacterial pathogens as well as common bacteria. The development of new antibiotics by major pharmaceutical companies has been relatively uncommon even as drug-resistant bacteria have emerged. Among the work that will be done at UF is a technique known as the hollow fiber infection model, which allows scientists to model changes in drug concentrations over time, as they would occur in humans.
“We can actually study how a drug kills the bacterium and also how it prevents or suppresses the emergence of antibiotic resistance. It’s another arrow in the quiver of drug development,” said George L. Drusano, M.D., a professor and director of the Institute for Therapeutic Innovation.
UF is one of the few universities in the country with the combination of specialized research equipment and evaluative tools for testing new antibiotics, according to Drusano. Then, there is UF’s human expertise: The research will rely on complex mathematical models to optimize drug treatment and reduce drug-development risks and poor therapeutic outcomes. In the field of high-consequence bacterial pathogens, Drusano is one of a handful of mathematical experts worldwide.
He puts it more modestly and succinctly: “I’m the one who does the fancy math.”
Curza will have a significant scientific challenge of its own — making chemical changes to the compounds that will be tested in UF Health’s laboratories. Late-stage testing in preclinical models will be done at a Department of Defense laboratory.
“The COVID-19 virus pandemic has also heightened awareness of the deficiencies in our current arsenal of antibacterial drugs,” said John W. Kozarich, CEO of Curza. “We are excited to expand our collaboration with the Institute for Therapeutic Innovation to advance our antibacterial platform to include treatments for biothreat agents in addition to community and hospital associated antibiotic-resistant pathogens. If successful, these unique molecules will represent the first new class of antibiotics discovered in the last 60 years with activity against these pathogens.”
The seven- to nine-year project is an exciting way to make an important contribution to the health and safety of the American public, the researchers said. That will include demonstrating to federal officials that any new antibiotic is effective against engineered, airborne bacteria.
The chance to develop a new antibiotic for both strategic and broader public use is invigorating, said Bret K. Purcell, M.D., Ph.D., a research associate professor and applied therapeutics specialist for emerging pathogens at the Institute for Therapeutic Innovation.
“Once this compound is developed and approved, we hope that it can also be put to use against community-acquired or ventilator-associated pneumonias,” he said.