Cont, A. | bioRxiv Science

bioRxiv2022

Mechanoregulation of biofilm architecture promotes Pseudomonas aeruginosa antibiotic tolerance.

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.

microbiology↗

bioRxiv2020

Biofilms mechanically damage epithelia by buckling.

During chronic infections and in microbiota, bacteria predominantly colonize their hosts as multicellular structures called biofilms. Despite their ubiquity in vivo, we still lack a basic understanding of how they interact with biological tissues, and ultimately how they influence host physiology. A common assumption is that biofilms interact with their hosts biochemically. However, the contributions of mechanics, while being central to the process of biofilm formation, have been vastly overlooked as a factor influencing host physiology. Specifically, how biofilms form on soft, tissue-like materials remains unknown. Here we show that biofilms can deform soft substrates by transmission of internally-generated mechanical stresses. We found that biofilms from both Vibrio cholerae and Pseudomonas aeruginosa can induce large deformations of soft synthetic hydrogels. Using a combination of mechanical measurements and mutants in matrix components, we found that biofilms deform their substrates by simultaneous buckling and adhesion. Specifically, mechanical constraints opposing growth causes biofilm buckling, while matrix components maintaining surface adhesion transmit buckling forces to the substrate. Finally, we demonstrate that biofilms can generate sufficient mechanical stress to deform and disrupt soft epithelial cell monolayers, suggesting that these forces can damage a host independently of typical virulence factors. Altogether, our results illustrate that forces generated by bacterial communities play an important role not only in biofilm morphogenesis but also in host physiology, suggesting a mechanical mode of infection.

microbiology↗