UB pharmacy professors developing antibiotics to fight resistant bacteria

BUFFALO, N.Y. — Every year, more than 1 million infections occur within health care facilities in the United States. They are associated with nearly 100,000 deaths and between $28 billion and $33 billion in excess costs, according to the U.S. Department of Health and Human Services.

Gram-negative bacteria are the leading causes of these infections, which have become increasingly resistant to antibiotic treatment, notes Yanan (Nancy) Zhao, MD, PhD, an internationally recognized infectious disease and antimicrobial researcher who joined the faculty of the University at Buffalo School of Pharmacy and Pharmaceutic Sciences in March.

Zhao is working toward a solution: creating a novel antibiotic within the class called biamyxins (BMX).

“Antibiotic resistance is an overwhelming problem globally because the antibiotics pipelines are nearly completely depleted,” says Zhao, professor of pharmacy practice in the Division of Clinical and Translational Therapeutics (CTT). “Effective therapeutic agents available to treat patients, if they turn out to have a multidrug resistant infection, are few and far between these days.”

Among largest NIH grants for pharmacy school

Zhao was recently awarded a five-year, $3.9 million research project grant (R01) from the National Institutes of Health (NIH) to develop these powerful antibiotics. This is one the largest NIH grants awarded to the pharmacy school, notes Brian Tsuji, PharmD, professor and associate dean for clinical and translational sciences and the director of the Division of CTT.

The project’s co-investigator is Liang Chen, MD, PhD, who was also recruited to UB as a professor of clinical and translational therapeutics this spring.

“This grant is so important to our community to improve the care of patients infected with bacterial infections that have no viable treatment options,” Tsuji says. “Dr. Zhao and Dr. Chen have already brought significant innovation to our division, department and school in the translational sciences. I can’t think of a more prolific beginning, and I’m so very excited to see the future growth of Dr. Zhao’s program, which holds significant promise to push UB to new heights.”

How biamyxins work

BMX antibiotics work by binding tightly to a part of the bacterial outer membrane, which allows them to kill the bacteria effectively.

“Unlike polymyxins and their recent derivatives, we have made innovative structural designs to enable our compounds to efficiently bind the LPS [lipopolysaccharide] of both sensitive and colistin-resistant gram-negative pathogens,” Zhao explains.

The preliminary lead compound in development has shown promising properties with rodents, Zhao says. It fights vigorously against various gram-negative bacteria, including those resistant to colistin, a commonly used antibiotic of last resort, and it has a low toxicity to human cells.

“Renal toxicity is the biggest limitation to the polymyxin class molecules,” she says. “Erasing toxicity is the advantage I’m hoping to see with our drug.”

Impressive infectious disease experience

Zhao most recently served as an associate professor at Hackensack Meridian School of Medicine and associate member of the Center of Discovery and Innovation at Hackensack Meridian Health. Prior to this appointment, she was an assistant professor at the Public Health Research Institute of Rutgers University.

At the onset of the COVID-19 pandemic, Zhao invented a diagnostic test for COVID-19 that was approved by the Food and Drug Administration Emergency Use Authorization and used to screen more than 10,000 patients. Zhao also created a novel SARS-CoV-2 variant screening tool, which was integrated into the New Jersey Department of Health’s COVID surveillance program.

“I have a passion for caring for patients,” Zhao says, “which is why we’re working on developing this new class of antibiotics to save lives.”

Meanwhile, Chen most recently served as associate professor at Hackensack Meridian School of Medicine and an associate member at Center of Discovery and Innovation. His research focuses on unraveling the molecular evolution of carbapenem-resistant Enterobacteriaceae (CRE), or “nightmare bacteria,” which has been classified as an urgent threat by the Centers for Disease Control and Prevention.

“The recruitment of Dr. Chen and Dr. Zhao serves as a major catalyst to create a ‘dream team’ of world-leading, NIH-funded investigators in translational therapeutics to combat the world’s most pressing problems in infectious disease and save countless lives,” says Gary Pollock, PhD, dean of the pharmacy school.

So far, Zhao’s and Chen’s antibiotic research has proven effective in mice and rats.

“We are very enthusiastic that we will create a novel drug candidate that meets the criteria to enter the investigational new drug enabling stage, which is a cornerstone of the drug development process,” Zhao says. “It helps researchers predict safety concerns and estimate safe and efficacious starting doses for clinical trials.”

She praised the pharmacy school, specifically Tsuji, Pollack, and William Prescott, chair of the Department of Pharmacy Practice, for their support in helping her make the transition to UB and land the NIH grant.

“Joining UB and working within this highly collaborative and vibrant environment has been a dream come true,” Zhao says. “Securing the R01 grant is the first significant milestone, and I am tremendously excited about the opportunities it presents and the future for advancing our research and contributing to UB’s aspirational goals.”