Engineering Microbial Physiology with Synthetic Polymers: Cationic Polymers Induce Biofilm Formation in Vibrio cholerae and Downregulate the Expression of Virulence Genes.

Abstract

Vibrio cholerae, the causative agent of cholera, is an abundant environmental bacterium that can efficiently colonize the intestinal tract and trigger severe diarrheal illness. Motility, and the production of colonization factors and cholera toxin, are fundamental for the establishment of disease. In the aquatic environment, V. cholerae persists by forming avirulent biofilms on zooplankton, phytoplankton and chitin debris. Here, we describe the formation of artificial, biofilm-like communities, driven by exposure of planktonic bacteria to synthetic polymers. This recruitment is extremely rapid and charge-driven, and leads to the formation of initial \"seed clusters\" which then recruit additional bacteria to extend in size. Bacteria that become entrapped in these \"forced communities\" undergo transcriptional changes in motility and virulence genes, and phenotypically mimic features of environmental biofilm communities by forming a matrix that contains polysaccharide and extracellular DNA. As a result of this lifestyle transition, pathogenicity and in vivo host colonization decrease. These findings highlight the potential of synthetic polymers to disarm pathogens by modulating their lifestyle, without creating selective pressure favoring the emergence of antimicrobial resistant strains.