A New Paradigm of Developing Therapeutics to Infectious Diseases by Combining Insights from Nature and Engineering

Abstract

Broad host-spectrum antibiotics not only kill pathogens, but also beneficial commensal bacteria of the host microbiome that play crucial roles for health. In Nature, bacteria kill other bacteria much more selectively than antibiotics do. Because there is metabolic cost involved in producing molecules to inhibit others, evolution endowed bacteria with bacteriocins to kill those who are similar enough to compete for the same niche, while leaving more distantly related bacteria, intact. The presence of such narrow host-spectrum antibacterial molecules suggests that by engineering and reprogramming what is found in nature, it may be possible to develop highly effective yet selective therapeutics to infectious diseases, either as purified drugs, or as live bacterial therapeutics. Here, I propose a new paradigm of developing highly selective therapeutics by combining insights from Nature and engineering and applied this against foodborne pathogens, one of the most common causes of bacterial infections for humans.

Bacterial pore-forming toxins

“…Another study demonstrated that microcapsule delivery of the active form of colicin Ia reduced E. coli colonisation in murine models [225]. Engineering of chimeric proteins and use of cocktails of different toxins could provide a greater spectrum of activity and reduce the risk of resistance developing in target bacteria [226]. Similarly, in recent years peptidic bacteriocins have shown great promise for their efficacy as alternative anti-microbials when administered in model organisms [227].…”