Biology subjects

Guillemin, K.

Publications and source records attributed to Guillemin, K..

3 recordsLinked to original sources

bioRxiv2018

Agent-Based Modeling Demonstrates How Local Chemotactic Behavior Can Shape Biofilm Architecture

Mature bacterial biofilms have elaborate three-dimensional architectures that endow these structures with their durability and resistance to environmental perturbations. We used agent-based modeling to explore whether local cellular interactions were sufficient to give rise to global structural features of biofilms. Specifically, we asked whether chemorepulsion from a self-produced quorum-sensing molecule, autoinducer-2 (AI-2), was sufficient to recapitulate biofilm growth and cellular organization observed for biofilms of the human pathogen Helicobacter pylori. To carry out this modeling, we modified an existing platform, Individual-based Dynamics of Microbial Communities Simulator (iDynoMiCS), to incorporate three-dimensional chemotaxis, planktonic cells that could join or leave the biofilm structure, and cellular production of AI-2. We simulated biofilm growth of previously characterized H. pylori strains with varying AI-2 production and sensing capacities. Using biologically plausible parameters, we were able to recapitulate both the variation in biofilm mass and cellular distributions observed with these strains. Specifically, the strains that were competent to chemotax away from AI-2 produced smaller and more heterogeneously spaced biofilms, whereas the AI-2 chemotaxis defective strains produced larger and more homogeneously spaced biofilms. The model also provided new insights into the cellular demographics contributing to the biofilm patterning of each strain. Our analysis supports the idea that cellular interactions at small spatial and temporal scales are sufficient to give rise to larger scale emergent properties of biofilms.\n\nImportanceMost bacteria exist in aggregated, three-dimensional structures called biofilms. Biofilms are resistant to antimicrobials and can pose societal problems, for example when they grow in plumbing systems or on medical implants. Understanding the processes that promote the growth and disassembly of biofilms could lead to better strategies to manage these structures. We had previously shown that Helicobacter pylori bacteria are repulsed by high concentrations of a self-produced molecule, autoinducer-2 (AI-2) and that H. pylori mutants deficient in AI-2 sensing form larger and more homogeneously spaced biofilms. Here we used computer simulations of biofilm formation to show that local H. pylori behavior of repulsion from high AI-2 could explain the overall architecture of H. pylori biofilms. Our findings demonstrate that it is possible to change global biofilm organization by manipulating local cell behaviors, which suggests that simple strategies targeting cells at local scales could be useful for controlling biofilms in industrial and medical settings.

microbiology↗

bioRxiv2018

Bacterial cohesion predicts spatial distribution in the larval zebrafish intestine

Are there general biophysical relationships governing the spatial organization of the gut microbiome? Despite growing realization that spatial structure is important for population stability, inter-bacterial competition, and host functions, it is unclear in any animal gut whether such structure is subject to predictive, unifying rules, or if it results from contextual, species-specific behaviors. To explore this, we used light sheet fluorescence microscopy to conduct a high-resolution comparative study of bacterial distribution patterns throughout the entire intestinal volume of live, larval zebrafish. Fluorescently tagged strains of seven bacterial symbionts, representing six different species native to zebrafish, were each separately mono-associated with animals that had been raised initially germ-free. The strains showed large differences in both cohesion--the degree to which they auto-aggregate--and spatial distribution. We uncovered a striking correlation between each strains mean position and its cohesion, whether quantified as the fraction of cells existing as planktonic individuals, the average aggregate size, or the total number of aggregates. Moreover, these correlations held within species as well; aggregates of different sizes localized as predicted from the pan-species observations. Together, our findings indicate that bacteria within the zebrafish intestine are subject to generic processes that organize populations by their cohesive properties. The likely drivers of this relationship, peristaltic fluid flow, tubular anatomy, and bacterial growth and aggregation kinetics, are common throughout animals. We therefore suggest that the framework introduced here, of biophysical links between bacterial cohesion and spatial organization, should be useful for directing explorations in other host-microbe systems, formulating detailed models that can quantitatively map onto experimental data, and developing new tools that manipulate cohesion to engineer microbiome function.

microbiology↗

bioRxiv2017

Modernized tools for streamlined genetic manipulation of wild and diverse symbiotic bacteria

The capacity to associate symbiotic bacteria with vital aspects of plant and animal biology is outpacing our understanding of the mechanisms shaping these interactions. A major barrier to mechanistic studies is the paucity of tools for genetically manipulating wild and diverse bacterial isolates. Solving this problem is crucial to elucidating the cellular and molecular rules that govern symbiotic relationships and ultimately harnessing them for agricultural and biomedical applications. Therefore, we constructed a series of vectors that expedite genetic knock-in and knock-out procedures across a range of bacterial lineages. This was accomplished by developing strategies for domestication-free bacterial conjugation, designing plasmids with customizable features, and streamlining allelic exchange using visual markers of homologous recombination. These tools enabled a comparative study based on live imaging of diverse bacterial symbionts native to the zebrafish intestine, with which we discovered heterogeneous colonization patterns and a striking correlation between bacterial population biogeography and cellular behavior.

genetics↗