Avidocin™ & Purocin™ proteins
Naturally occurring R-type bacteriocins have evolved to defensively kill specific strains of competing bacteria. These proteins employ single-hit kinetics, that is, a single bacteriocin can kill a bacterium, making them extraordinarily potent. Pylum has developed a technology platform to enable engineering these bacteriocins to specifically target different, threatening bacteria.
Avidocin proteins are engineered to bind to unique molecules on the surface of the intended target bacteria. By zeroing in on these unique surface signatures of their bacterial targets, Avidocin proteins do not bind to or damage off-target bacteria. The ability to engineer Avidocin proteins to target most any bacteria based on characteristics unique to the species or even the strain allow for:
- Potent and targeted treatments – An Avidocin protein will kill only the targeted bacteria and not other bacteria, thereby avoiding damage to off-target species.
- Tailorable – Avidocin proteins can be rapidly designed to kill virtually any bacterium, gram positive or negative.
- Ignoring antibiotic resistance – Avidocin proteins are unaffected by mechanisms of antibiotic-resistance and accordingly, kill drug-resistant bacteria.
- Targeting surface accessible virulence or fitness factors – The rare bacteria emerging resistant to the targeted Avidocin protein will have lost their surface target and thereby compromised their virulence or fitness.
As a result of their highly targeted nature, Avidocin proteins cause minimal unintended collateral damage to the important, health-promoting bacteria within each person. Avidocin™ therapeutics consist of normal amino acids, do not contain any DNA, and do not trigger the release of toxins upon killing the target bacteria.
As a result, there is minimal or no disruption to the surrounding microbiota, which recent studies have found to be critical for restoring and maintaining the natural, healthy diversity within the gut microbiota.
Like Avidocin proteins, Purocin proteins bind to unique target molecules on the surface of the target bacteria and promptly kill. This allows the Purocin therapeutics to be extremely specific against selected strains of pathogenic bacteria without unintended damage to the healthy commensal bacteria. The therapeutics also destroy bacteria with a unique mechanism of action that enables the killing of antibiotic-resistant bacteria.
Laboratory research has shown Purocin proteins not only to be highly potent against targeted bacteria but non-toxic and biodegradable. Pylum is currently developing additional Purocin™ proteins for food safety, including those targeting E. coli, Salmonella, and Listeria.
Purocin proteins due to their great specificity and apparent safety offer a promising new technology for protecting the food supply from bacterial contaminants. Purocin proteins can be created to kill specific, threating bacteria, reducing the need for broad-spectrum antibiotics and chemicals.
Outbreaks of bacterial food contamination have brought global awareness to E. coli strains in hamburger, spinach, and sprouts; Salmonella in eggs and poultry; and Listeria in dairy products. These contaminations have become a growing problem that is compounded by the increasing resistance of many of these bacteria to antibiotics.
Cryo-EM structure of an R-type bacteriocin showing the sheath, baseplate, and partial tail fibers (Ge et al., 2015).
Cryo-EM structure showing the internal core and sheath of the R-type bacteriocin (Ge et al., 2015).