11:42pm Thursday 17 October 2019

UNMC researcher bridges antibiotic gap in major breakthrough

by Tyler Scherr, UNeMed

Gus Wang, Ph.D., an associate professor in the UNMC Department of Pathology and Microbiology and a world-leading expert on antimicrobial peptides, has published a field-altering discovery in the Proceedings of the National Academy of Sciences of the United States, widely regarded as one of the most prestigious academic journals.

Using Dr. Wang’s world-renown peptide database, the UNMC team deduced previously unknown peptide properties that govern efficacy inside a living animal.

Researchers have long known that antimicrobial peptides have therapeutic potential against antibiotic-resistant bacterial infections, particularly with topical treatments for things like skin infections. Unfortunately, the tiny protein fragments are also fragile and are much less effective inside the body for things like blood infections.

But bacteria are also less likely to develop resistance to peptides. Researchers around the world have long looked at antimicrobial peptides as a potential solution to resistance.

Until now, it seems, no one has been able to make antimicrobial peptides work in a broad, therapeutic way.

“Researchers have largely been so excited with the potential of these peptides for treating infections that they rushed forward with efficacy testing and clinical trials,” Dr. Wang said. “This paper is important to the field because it suggests that certain peptides are less sticky to host cells, and therefore are more likely to work in vivo. This exciting discovery represents a paradigm shift in antimicrobial peptide design, and may lead to novel peptides with broader therapeutic potential.”

Dr. Wang and his team designed an algorithm to identify and classify numerous antimicrobial peptide properties. From this algorithm, Dr. Wang and his postdoctoral fellow, Biswajit Mishra, Ph.D., were able to design and test idealized peptide sequences against the most notorious drug-resistant pathogens. That work was previously published in the Journal of the American Chemical Society.

With high-efficacy candidates in hand, they systematically altered the peptide sequences, one amino acid at a time, and repeated efficacy testing. They also effectively tested their spectrum of sequences in a mouse model of systemic infection, with the help of postdoc Jayaram Lakshmaiah Narayana, Ph.D.

Dr. Wang’s results were published in the online version of the Proceedings of the National Academy of Sciences of the United States.

His method of designing systemically active peptides — along with the initial key amino acid sequences — is in the patent process through UNeMed, the technology transfer and commercialization office at UNMC and UNO. Several pharmaceutical companies have expressed interest in the technology as a therapeutic for both human and animal health.

 

University of Nebraska Medical Center

 


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