(4cd) A Molecular Engineering Approach Against Bacterial Biofilms and Spores

A Molecular Engineering Approach against Bacterial Biofilms and Spores

Biofilms and spores are the ultimate survival mechanisms of bacterial cells against harsh environments. Both of them defy conventional antibiotic treatments, and both of them can lead to serious clinical consequences, e.g. cystic fibrosis (CF) and B.anthrax infection. Here we present novel molecular engineering approaches to combat these pressing biological threats.

For bacterial biofilms, the critical step lies in the prevention of initial bacterial adhesion and subsequent surface proliferation. To this end, zwitterionic polymer-based nonfouling materials were designed and synthesized that not only can resist bacterial adhesion via polymer hydration but also carry additional biological functions, particularly the controlled release of antimicrobial agent as counter ions or leaving groups to inhibit bacterial growth close to the surface. In addition to the integration of nonfouling and antimicrobial properties,  well-defined zwitterionic copolymer structures were also synthesized by means of living polymerization that are thermo- or pH- responsive, making them suitable for specific biomedical applications including wound dressing and biosensing.

For bacterial spores, the existing industrial approach relies on concentrated hydrogen peroxide solution for sterilization, which is dangerous to human as well as toxic to the environments. To remedy this obvious shortcoming, we resort to the fundamental study of dodecylamine (DDA) lethal germination mechanism. DDA was arguably the strongest antispore agent known to date that can trigger spore germination followed by inactivation at low concentration and under near ambient temperature. However, the human toxicity of DDA limited its application outside the realm of academic study. By unveiling the DDA mechanism of action, we were able to grasp the key structural features central to its bioactivity and formulate molecular principles to guide the design of novel antispore molecules. We have so far experimentally demonstrated that the by applying our molecular understanding we can successful design and discover molecules that possess strong antispore activities.