Generalizable and Non-genetic Approach to Create Metabolically-active-but-non-replicating Bacteria

Abstract

Researchers at the University of California, Davis have developed a method to stop bacterial growth while maintaining desirable metabolic functions for therapeutic and biotechnological applications.

Full Description

Recent understanding of the human microbiome has ushered in the interest in engineering bacteria or probiotics for therapeutic applications. Yet, few if any engineered bacteria have been approved by FDA for therapeutic applications. For many target applications, it is difficult to maintain the desirable characteristics and metabolic processes of bacteria while simultaneously restricting their replication in non-targeted parts of a patient and the human population at large. The existing approach to limit cellular division often involves genetically modifying bacteria, but this is a technically challenging process and does not usually generalize to non-standard bacteria. Furthermore, such genetic modification tends to induce stress on the bacteria, resulting in poor therapeutic performance. In addition, bacteria can mutate the genetic control elements, resulting in biocontainment issues. A generalizable method of limiting bacterial growth while keeping their metabolic functions is needed to translate bacterial vaccines and probiotics in clinical applications.

Researchers at the University of California Davis have developed a non-genetic method to selectively limit cellular division. This process causes an irreversible stop of bacterial growth but still allows for the typical metabolic activity, nutrient import, protein synthesis, and motility that are desired for therapeutic applications. Additionally, the process results in cells that are robust to certain external stress factors. The novel approach allows for the generation of broad metabolically-active-but-non-replicating bacterial classes, including Staphylococcus, Pseudomonas, Klebsiella, Escherichia, Lactobacillus, etc. The metabolically-active-but-non-replicating bacteria can be used for vaccine, anti-cancer, and gastro-intestinal applications.

Applications

• Living therapeutics 
• Gene delivery vectors 
• Live attenuated vaccines 
• Biosensors 
• Probiotics

Features/Benefits

• Improved stability and cellular functions compared to genetic modifications
• Generalizable for many different bacterial strains

Patent Status