Design Principles of the Microbiome

 Spatial Organization of the Microbiome

The human microbiome is an assemblage of diverse bacteria that interact with one another to design a community. Rapid availability of nutrition and protection from antibiotics are some advantages of a specific spatial niche within a microbial community. The mechanisms that drive microbial interactions and guide the architecture of microbial communities are unclear. 
 
To learn more about collective behavior, we investigated the swarm properties of gliding bacteria from the human oral microbiome and their relevance on the spatial organization of polymicrobial communities. We found that cells of non-motile bacterial species from the human oral microbiome attached to gliding bacteria. The non-motile bacteria were  propelled as cargo along the length of a gliding cell. The cargo looped from one pole to the other of the motile gliding cell. A lectin domain containing motile cell-surface adhesin SprB keeps the cargo attached to the transporter.  Movie 1. A bacterium Prevotella oris moving as cargo over a rod-shaped Capnocytophaga gingivalis (transporter) cell 
 
Multi-color fluorescent spectral imaging of cells of seven different live but non-motile bacterial species that are abundant in the human oral microbiome revealed their long-range transport in a polymicrobial community by a swarm of gliding bacteria. The swarms moved in a circular fashion in the 2D plane and are layered on top of one other in 3D space. We found that the synchronized public transportation of non-motile cargo bacteria helps shape a microbial community (Shrivastava et al PNAS, 2018). At present, efforts are underway to understand design principles of the microbiome. This project is funded by a NIH-NIDCR K99/R00 award to A.S.
 
             Movie 2. A live microbial community being shaped via the active transport of cargo                       
 

 

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A Rotary Motor Drives Bacterial Gliding

Bacteria that swim are driven forward by helical filaments that rotate like propellers. The number and location of filaments vary among different bacteria, yet the core mechanism remains the same. In contrast, motile but non-swimming bacteria do not have propellers, yet they achieve efficient self- propulsion over surfaces. Such movement is divided into two categories: (i) twitching and (ii) gliding. Twitching involves the extension and retraction of type IV pili and gliding involves movement of cell-surface adhesins along the length of a cell.
 
Bacteria of the phyla Bacteroidetes are found in the human oral and gut microbiome, lakes, oceans, and the plant rhizosphere. Some human-associated Bacteroidetes have the ability to glide. We found that gliding bacteria have a novel rotary motor that generates high torque (Shrivastava et al. Curr. Biol. 2015). Tethered cells pinwheel around a fixed axis (Movie 3). This work expanded the catalog of biological rotary motors, which now includes three motors: the Fo ATP synthase, the bacterial flagellar motor, and the gliding motor. 
 
Movie 3. A tethered Flavobacterium cell rotating around a fixed axis.
 
 

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The Biological Design of a Self-propelled Screw

How a rod-shaped bacterial cell moves over a surface is a question that has fascinated biologists and physicists for a long time. Bacteria live in the low Reynolds number regime hence they must encounter negligible inertia. In order to move in a particular direction, gliding bacterial cell must generate force. Gliding bacteria have a cell-surface adhesin SprB, which is known to move along the length of a cell. We cross-linked a gold nanoparticle to SprB, imaged it's motion in 3D space and found that SprB moves in a spiral fashion. Using experimental and theoretical tools, we found that a gliding bacterium works as a self-propelled screw, with a cell-surface adhesin moving along its external threads (Shrivastava et al., Biophysical J., 2016).
 
                                                      3D view of the Track along which SprB moves
Movie 4. 3D view of a track along which SprB moves
 

 

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The Type 9 Protein Secretion System Enables Motion 

An active type 9 protein secretion system (T9SS) is required for gliding. Some of our earlier work showed that bacteria secrete cell-surface adhesins such as SprB via T9SS. We characterized the core T9SS proteins (Shrivastava et al. J. Bacteriol. 2013). Our recent data suggests that a molecular rack and pinion machinery actuates gliding. In this assembly, T9SS localizes near the rotary motor (Shrivastava and Berg, Science Advances, 2020).