Mechanoregulation of biofilm architecture promotes Pseudomonas aeruginosa antibiotic tolerance.

Abstract

In the wild, bacteria are most frequently found in the form of multicellular structures called biofilms1. Biofilms grow at the surface of abiotic and living materials with wide-ranging mechanical properties. Despite their co-occurrence during infection, we still lack a clear understanding of how mechanics regulate biofilm architecture and the physiology of resident bacteria. The opportunistic pathogen Pseudomonas aeruginosa forms biofilms on indwelling medical device2 and on soft tissues including burn wounds and the airway mucosa3. Here, we demonstrate that mechanical properties of hydrogel material substrates define P. aeruginosa biofilm architecture. We show that hydrogel mesh size regulates twitching motility, a surface exploration mechanism priming biofilms, ultimately controlling the arrangement of single cells in the multicellular community. The resulting architectural transitions increase P. aeruginosas tolerance to colistin, a last resort antibiotic. Our results thereby establish material properties as a regulator of biofilm architecture and antibiotic efficacy.