Production Increases for Pyocin S5, Potential Antibiotic for Treating Lung Disease

Production Increases for Pyocin S5, Potential Antibiotic for Treating Lung Disease
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Project GAIA, establishing a large-scale manufacturing process for Pyocin S5, an investigational antibiotic for the treatment of lung disease in people who have cystic fibrosis, is now complete.

The scale-up process for Pyocin S5 manufacturing was performed by CPI, an independent technology innovation center in the U.K. This work will enable the University of Glasgow, which first developed the small-scale process, to advance the clinical evaluation of this potential treatment.

“Thanks to the state-of-the-art facilities and expert teams at CPI, we now have a scaled-up process to produce larger quantities of Pyocin S5. This will allow us to progress our preclinical evaluation of a treatment that could have a positive impact on the lives of those with cystic fibrosis,” Dan Walker, PhD, associate professor of bacteriology at the University of Glasgow, said in a press release.

Lung infection with Pseudomonas aeruginosa bacteria is the main cause of death among patients with cystic fibrosis. With current antibiotics failing to protect against hard-to-treat bacteria, the need for alternative therapies is high.

Using recombinant (man-made) Escherichia coli bacterial cells, a group of researchers at the University of Glasgow produced Pyocin S5, a protein antibiotic that can kill P. aeruginosa bacteria.

Previous studies with cells in the lab (in vitro) and in live animals (in vivo) have shown that Pyocin S5 is highly effective and potent, when compared to the antibiotics currently used in the clinic to treat bacterial infections.

Nonetheless, the small-scale production process implemented by researchers at the University of Glasgow needed to be scaled up to produce larger quantities of the Pyocin S5 protein antibiotic to allow for its clinical evaluation.

The scale-up project, developed at CPI’s National Biologics Centre, in Darlington, included the establishment and optimization of upstream and purification processes, the development of analytical techniques and a three-month study assessing the therapy’s stability.

Using high-throughput screening — a technique that allows scientists to look at a vast number of factors in a short period — the teams at CPI were able to rapidly identify optimal conditions for large-scale protein production in a few days, accelerating process development and establishing a defined, large-scale manufacturing route for Pyocin S5.

Furthermore, CPI was able to significantly improve the production yield —  from one liter small batch to a microbial fermentation process that can produce 100 liters of product. The scale-up work also provided important information that can be used in future toxicology studies, the next step in clinical evaluation, which will allow accelerated production of Pyocin S5.

“This partnership with the University of Glasgow has been extremely positive and we at CPI are pleased with its success. Ultimately, it has enabled the progression of a treatment for cystic fibrosis that otherwise may not have been possible,” said Lucy Foley, director of biologics at CPI.

Diana holds a PhD in Biomedical Sciences, with specialization in genetics, from Universidade Nova de Lisboa, Portugal. Her work has been focused on enzyme function, human genetics and drug metabolism.
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Patrícia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Diana holds a PhD in Biomedical Sciences, with specialization in genetics, from Universidade Nova de Lisboa, Portugal. Her work has been focused on enzyme function, human genetics and drug metabolism.
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