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Pylum Biosciences Collaborates on Research Published in the Journal Nature

April 15, 2020 Off By BusinessWire

— Paper Reveals Structure of Naturally Occurring Protein Complex Used to Recognize and Kill Bacteria —

— New Understanding Broadens Engineering Insights for Designing Precision Antibacterial Agents —

— Pylum Developing Precisely Targeted Antibacterial Agents to Selectively Kill Invasive Bacteria While Preserving the Healthy Microbiome of the Digestive System —

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Pylum Biosciences, Inc., a biotechnology company developing a new class of precision antibacterial medicines, in collaboration with researchers at the University of California, Los Angeles and The University of Texas Medical Branch, today announced the publication of key structural mechanisms of action for a class of naturally occurring bacteria killers, R-type pyocins.

Pioneering a New Class of Precision Antibiotics

R-type pyocins are naturally occurring complex bactericidal proteins produced by bacteria to kill competing strains of bacteria. By leveraging the innate ability of pyocins, Pylum has built a proprietary platform to engineer a novel class of antibacterial agents, termed Avidocin™ proteins, that are highly specific, stable and targetable with the potential to treat drug-resistant bacteria. Developing new classes of antibacterial agents is critical, as globally, few options exist for resolving drug-resistant infections.

“While COVID-19 is at the forefront of everyone’s mind, bacteria have also rapidly spread across the globe,” said James Knighton, Chairman of Pylum Biosciences. “Our robust platform technology allows us to move from detection of a novel bacteria to a narrow-spectrum bactericidal design in a period of weeks. With a dearth of antibiotic programs today and antibiotic-resistant bacterium already causing more than two million infections a year in the United States alone, we believe it is imperative to create new medicines so society can be well prepared for a drug-resistant bacterial outbreak of proportions yet unseen.”

Nature Publication Reveals Structure of Bacterial Killers

Online today, the publication in Nature entitled ‘Action of minimal contractile bactericidal nanomachine,’ demonstrates how a team of researchers analyzed the R-type pyocin molecule to determine how it sabotages invading bacteria. A video demonstrating how R-type pyocins work within the body, illustrating the work of the publication, can also be viewed on the Nature website.

“This work elucidates the specific mechanism of action for R-type pyocin, revealing structural components both through imaging and experimentation,” said Petr Leiman, Ph.D., Associate Professor at the University of Texas and co-author of the paper. “We were able to demonstrate, for the first time, what efficient bacteria killers these nanomachines called pyocins are.”

“We used advanced tools, including X-ray crystallography and cryo electron microscopy, to image pyocin activity,” commented Z. Hong Zhou, Ph.D., Professor in the Microbiology, Immunology, and Molecular Genetics at University of California, Los Angeles and a senior author of the paper. “The images truly illuminated how complex and intricate these molecules are and should help future bio-engineering efforts.”

Designing Antibacterial Agents for the Future

Pylum researchers have engineered pyocins to create the Avidocin™ platform, a proprietary class of precisely targeted agents that can kill bacteria. Importantly, Avidocin™ proteins can be readily re-engineered to target a range of bacteria. The critical connection between specific recognition of the correct target and deployment of bactericidal activity is at the core of Avidocin™ technology. Understanding how this works at an atomic level now gives Pylum the further knowledge to fine tune the sensitivity as well as specificity of its precision proteins.

“By focusing on narrow-spectrum agents that exquisitely kill only one type of bacteria, we believe we reduce the risk of widespread resistance that has rendered many broad-spectrum antibiotics useless, and at the same time spare the healthy microbiota,” said Dean Scholl, Ph.D., Vice President of Research at Pylum and co-author of the paper. “Our technology has demonstrated potent activity in a number of in vivo models. We are currently in the process of scaling up production with a goal of beginning clinical development.”

About the Avidocin™ Platform

Avidocin™ proteins are highly potent and precise antibacterial agents that can be engineered to target virtually any bacteria, including those that are antibiotic-resistant, without damaging the helpful resident bacteria necessary in a healthy microbiota. Avidocin™ proteins are engineered R-type bacteriocins (pyocins), naturally occurring defensive proteins of bacteria, that target a specific strain of bacteria. For example, one Avidocin specifically targets vancomycin-resistant Enterococcus. In addition, multiple in vivo studies have shown that Avidocin™ proteins protect against bacterial infection and data demonstrate that Avidocin™ proteins destroy C. difficile, Pseudomanas or E. coli while healthy gut bacteria were not detectably disturbed.

About Pylum Biosciences

Pylum Biosciences has developed a unique technology, known as the Avidocin™ platform. Avidocin™ proteins, a new class of narrow-spectrum bacteria-killing agents, offer a potential solution to overcome two key problems with broad-spectrum antibiotics: the rampant spread of drug resistance and the unintended damage to healthy protective bacteria that comprise the microbiota. For more information on Pylum Biosciences, visit the company’s website at www.pylumbio.com

Avidocin™ is a trademark of Pylum Biosciences.