Research

Our research interests mainly revolve around force generation by bacteria:

• The type and magnitude of forces they can exert.
• The mechanisms at play for exerting such forces.
• The role of those forces in the interaction between bacteria and between bacteria and host cells. 

During the last decade, the importance of physical forces in the biological world has come to be better realized, mostly due to the development of the proper tools. We use and develop such techniques intended to measure and apply physical forces at the right scale and amplitude, like optical tweezers, magnetic tweezers or polyacrylamide micropillars (PoMPs). Paired with more mainstream techniques, like molecular biology, proteomics, genomics, biochemistry or surface chemistry, they enable us to peer into bacterial mechanobiology.

Our model system of choice is the genetically tractable and sequenced organism Neisseria gonorrhoeae (or GC for Gonococcus), the causative agent of Gonorrhoeae. GC bacteria harbor appendages shared with many bacteria: Type IV pili (Tfp). Tfp are long (up to 30 μm) and thin (diameter of 6 nm) dynamic polymers that emanate from the surface of GC. Tfp undergo cycles of elongation and retraction. While retracting, a single pilus can exert forces of 100 pN. These retractable filaments are implicated in a wide range of functions (DNA uptake, motility, cell infectivity, biofilm formation…), but the mechanisms responsible for many of those functions still need to be defined. And force seems to play an important role in them. 

Cooperative bundling of pili A lone GC bacterium can exhibit close to 100 pili on its surface which can pull surrounding bacteria into tightly  aggregated microcolonies of 10-1000 bacteria (see adjacent Electron Microcopy image). The use of a micropillar assay we designed (see adjacent schematic) along with fluorescent and electronic microscopy demonstrated that bacteria can pull in unison bundles of up to 10 pilus fibers and generate forces up to 1 nN that can be maintained for hours. This forces are quite huge at this scale. They represent roughly 100,000 times the bodyweight of the bacterium. This fact led a few journalists to dub GC the "strongest organism"(here, here or here). Lesser forces are known to be sufficient to distort the cortex of human cells and indeed GC bacteria are able to generate extreme rearrangements of their host cells cortex, triggering at the same time many signaling pathways.

Force dependent polymorphism Using a combination of techniques including optical and magnetic tweezers, electron
microscopy, immunofluorescence, molecular biology, Atomic Force Microscopy and molecular combing, we discovered that Tfp can undergo a structural transition when subjected to defined forces. When submitted to 100 pN of force, a single pilus fiber can transition to adopt a new quaternary structure, 3 times longer and 40% narrower than that of the original (see adjacent Electron Microscopy image). Interestingly, this new extended conformation of Tfp possesses different immunogenic properties. Epitopes hidden in the core of the original structure are exposed in this new, extended structure (seeadjacent  immunofluorescence image). This transition exemplifies the extreme plasticity of Tfp filaments. In association with the ability for Tfp to undergo antigenic variation, to possess minor pllins and to harbor various post-translational modifications, this structural transition can begin to explain the wide range of functions that Tfp are involved with.