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Persat, A.

Publications and source records attributed to Persat, A..

22 records · Page 2Linked to original sources

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↗

Filamentation of Vibrio cholerae is an adaptation for surface attachment and biofilm architecture

Collective behavior in spatially structured groups, or biofilms, is the norm among microbes in their natural environments. Though microbial physiology and biofilm formation have been studied for decades, tracing the mechanistic and ecological links between individual cell properties and the emergent features of cell groups is still in its infancy. Here we use single-cell resolution confocal microscopy to explore biofilm properties of the human pathogen Vibrio cholerae in conditions closely mimicking its marine habitat. We find that some - but not all - pandemic isolates produce filamentous cells than can be over 50 m long. This filamentous morphotype gains a profound competitive advantage in colonizing and spreading on particles of chitin, the material many marine Vibrio species depend on for growth outside of hosts. Furthermore, filamentous cells can produce biofilms that are independent of all currently known secreted components of the V. cholerae biofilm matrix; instead, filamentous biofilm architectural strength appears to derive from the entangled mesh of cells themselves. The advantage gained by filamentous cells in early chitin colonization and growth is counter-balanced in longer term competition experiments with matrix-secreting V. cholerae variants, whose densely packed biofilm structures displace competitors from surfaces. Overall our results reveal a novel mode of biofilm architecture that is dependent on filamentous cell morphology and advantageous in environments with rapid chitin particle turnover. This insight provides concrete links between V. cholerae cell morphology, biofilm formation, marine ecology, and - potentially - the strain composition of cholera epidemics.

microbiology↗

Cellular advective-diffusion drives the emergence of bacterial surface colonization patterns and heterogeneity

Microorganisms navigate and divide on surfaces to form multicellular structures called biofilms, the most widespread survival strategy found in the bacterial world1-4. One common assumption is that cellular components guide the spatial architecture and arrangement of multiple species in a biofilm. However, bacteria must contend with mechanical forces generated through contact with surfaces under fluid flow, whose contributions to colonization patterns are poorly understood. Here, we show how the balance between motility and flow promotes the emergence of morphological patterns in Caulobacter crescentus biofilms5. By modeling transport of single cells by flow and Brownian-like swimming, we show that the emergence of these patterns is guided by an effective Peclet number. By analogy with transport phenomena we show that, counter-intuitively, fluid flow represses mixing of distinct clonal lineages, thereby affecting the interaction landscapes between biofilm-dwelling bacteria. This demonstrates that hydrodynamics influence species interaction and evolution within surface-associated communities.

biophysics↗

Label-free visualization of type IV pili dynamics by interferometric scattering microscopy

Type IV pili (TFP) are slender objects that assemble by polymerization and secretion of protein subunits from bacterial cell surfaces. The mechanisms by which these surface structures of microscopic length and molecular diameter modulate the physical interaction of bacteria with their environment, however, remains poorly understood largely due to limitations in our ability to monitor and characterize the dynamics of individual TFP. Here, we demonstrate that interferometric scattering microscopy (iSCAT) enables label-free and dynamic visualization of TFP in intact cells of the opportunistic pathogen Pseudomonas aeruginosa. As a result, we can directly monitor extension, attachment and retraction events on millisecond timescale and nanometer length scale in three dimensions. These capabilities allow us to observe that P. aeruginosa is able to crawl against the direction of flow using short TFP filaments. Also, careful observation show that TFP retract rapidly after surface attachment, suggesting that P. aeruginosa senses contact of the pilus tip with the solid substrate. These results illustrate the power of iSCAT for the label-free visualization of small, dynamic microbial extracellular structures.

microbiology↗