(584au) The Search for Future Antispore Molecules

The bacteria spores have been known to survive under extreme environmental adversities, which include heat, UV, strong acidic/basic/oxidizing conditions as well as exposure to quaternary-ammonium-based antimicrobial compounds. The industrial approach towards spore disinfection using concentrated hydrogen peroxide solution is both dangerous to humans and harmful to the environment. The pathogenic nature of many bacterial spore species, e.g. B.anthrax, together with the lack of proper tools to combat this threat has motivated our research to search for novel antispore agents that are both safe and efficient.

To this end, a strategy combining mechanistic study with molecular design was devised to tackle this challenge. Our fundamental study starts with dodecylamine (DDA) lethal germination mechanism. DDA, arguably the strongest antispore molecule known, was reported to trigger spore lethal germination at low concentration and near ambient temperature. Unfortunately, the high toxicity to human has limited its general application outside the realm of academic study. Through our study on DDA mechanism of action, we were able to unveil the molecular principles behind its bioactivity and determine the key structural features essential to this process for the first time in over half a century. Furthermore, by applying this molecular level understanding, we were able to design new molecules from scratch that also show strong antispore activities. Through systematic evaluating these potential antispore agents, a balance can be found between antispore efficacy and environmental toxicity. The results of this study not only shed light on the nature of spore resistance, but also provide practical solutions to the biological threats faced by many clinical and industrial applications.