DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: A Microfluidics and Agent-Based Modeling Framework for Investigating Spatial Organization in Bacterial Colonies: The Case of Pseudomonas Aeruginosa and H1-Type VI Secretion Interactions

Abstract

The factors leading to changes in the organization of microbial assemblages at fine spatial scales are not well characterized or understood. However, they are expected to guide the succession of community development and function toward specific outcomes that could impact human health and the environment. In this study, we put forward a combined experimental and agent-based modeling framework and use it to interpret unique spatial organization patterns of H1-Type VI secretion system (T6SS) mutants of P. aeruginosa under spatial confinement. We find that key parameters, such as T6SS-mediated cell contact and lysis, spatial localization, relative species abundance, cell density and local concentrations of growth substrates and metabolites are influenced by spatial confinement. The model, written in the accessible programming language NetLogo, can be adapted to a variety of biological systems of interest and used to simulate experiments across a broad parameter space. It was implemented and run in a high-throughput mode by deploying it across multiple CPUs, with each simulation representing an individual well within a high-throughput microwell array experimental platform. The microfluidics and agent-based modeling framework we present in this paper provides an effective means by which to connect experimental studies in microbiology to model development. The work demonstratesmore » progress in coupling experimental results to simulation while also highlighting potential sources of discrepancies between real-world experiments and idealized models.« less

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); ORNL Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1437197
Alternate Identifier(s):
OSTI ID: 1423048
Grant/Contract Number:  
AC05-00OR22725
Resource Type:
Published Article
Journal Name:
Frontiers in Microbiology
Additional Journal Information:
Journal Name: Frontiers in Microbiology Journal Volume: 9; Journal ID: ISSN 1664-302X
Publisher:
Frontiers Media SA
Country of Publication:
Switzerland
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 97 MATHEMATICS AND COMPUTING; agent-based modeling; Pseudomonas aeruginosa; Type VI secretion; silicon microwell arrays; microbial succession; microbial organization; spatial confinement

Citation Formats

Wilmoth, Jared L., Doak, Peter W., Timm, Andrea, Halsted, Michelle, Anderson, John D., Ginovart, Marta, Prats, Clara, Portell, Xavier, Retterer, Scott T., and Fuentes-Cabrera, Miguel. A Microfluidics and Agent-Based Modeling Framework for Investigating Spatial Organization in Bacterial Colonies: The Case of Pseudomonas Aeruginosa and H1-Type VI Secretion Interactions. Switzerland: N. p., 2018. Web. doi:10.3389/fmicb.2018.00033.
Wilmoth, Jared L., Doak, Peter W., Timm, Andrea, Halsted, Michelle, Anderson, John D., Ginovart, Marta, Prats, Clara, Portell, Xavier, Retterer, Scott T., & Fuentes-Cabrera, Miguel. A Microfluidics and Agent-Based Modeling Framework for Investigating Spatial Organization in Bacterial Colonies: The Case of Pseudomonas Aeruginosa and H1-Type VI Secretion Interactions. Switzerland. https://doi.org/10.3389/fmicb.2018.00033
Wilmoth, Jared L., Doak, Peter W., Timm, Andrea, Halsted, Michelle, Anderson, John D., Ginovart, Marta, Prats, Clara, Portell, Xavier, Retterer, Scott T., and Fuentes-Cabrera, Miguel. Tue . "A Microfluidics and Agent-Based Modeling Framework for Investigating Spatial Organization in Bacterial Colonies: The Case of Pseudomonas Aeruginosa and H1-Type VI Secretion Interactions". Switzerland. https://doi.org/10.3389/fmicb.2018.00033.
@article{osti_1437197,
title = {A Microfluidics and Agent-Based Modeling Framework for Investigating Spatial Organization in Bacterial Colonies: The Case of Pseudomonas Aeruginosa and H1-Type VI Secretion Interactions},
author = {Wilmoth, Jared L. and Doak, Peter W. and Timm, Andrea and Halsted, Michelle and Anderson, John D. and Ginovart, Marta and Prats, Clara and Portell, Xavier and Retterer, Scott T. and Fuentes-Cabrera, Miguel},
abstractNote = {The factors leading to changes in the organization of microbial assemblages at fine spatial scales are not well characterized or understood. However, they are expected to guide the succession of community development and function toward specific outcomes that could impact human health and the environment. In this study, we put forward a combined experimental and agent-based modeling framework and use it to interpret unique spatial organization patterns of H1-Type VI secretion system (T6SS) mutants of P. aeruginosa under spatial confinement. We find that key parameters, such as T6SS-mediated cell contact and lysis, spatial localization, relative species abundance, cell density and local concentrations of growth substrates and metabolites are influenced by spatial confinement. The model, written in the accessible programming language NetLogo, can be adapted to a variety of biological systems of interest and used to simulate experiments across a broad parameter space. It was implemented and run in a high-throughput mode by deploying it across multiple CPUs, with each simulation representing an individual well within a high-throughput microwell array experimental platform. The microfluidics and agent-based modeling framework we present in this paper provides an effective means by which to connect experimental studies in microbiology to model development. The work demonstrates progress in coupling experimental results to simulation while also highlighting potential sources of discrepancies between real-world experiments and idealized models.},
doi = {10.3389/fmicb.2018.00033},
journal = {Frontiers in Microbiology},
number = ,
volume = 9,
place = {Switzerland},
year = {Tue Feb 06 00:00:00 EST 2018},
month = {Tue Feb 06 00:00:00 EST 2018}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.3389/fmicb.2018.00033

Citation Metrics:
Cited by: 14 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Pseudomonas entomophila and Pseudomonas mendocina: Potential models for studying the bacterial type VI secretion system
journal, August 2011


Superresolution Imaging of Intact Microbial Communities Reveals Molecular Architecture of Biofilm Development and Bacterial Organization
journal, February 2011


A Virulence Locus of Pseudomonas aeruginosa Encodes a Protein Secretion Apparatus
journal, June 2006


The effect of biofilm permeability on bio-clogging of porous media
journal, December 2011

  • Pintelon, Thomas R. R.; Picioreanu, Cristian; van Loosdrecht, Mark C. M.
  • Biotechnology and Bioengineering, Vol. 109, Issue 4
  • DOI: 10.1002/bit.24381

Micropatterned culture of HepG2 spheroids using microwell chip with honeycomb-patterned polymer film
journal, October 2014


Agent-based modeling of the complex life cycle of a cyanobacterium (Anabaena) in a shallow reservoir
journal, July 2008

  • Hellweger, Ferdi L.; Kravchuk, Elena S.; Novotny, Vladimir
  • Limnology and Oceanography, Vol. 53, Issue 4
  • DOI: 10.4319/lo.2008.53.4.1227

The spatial organization and microbial community structure of an epilithic biofilm
journal, December 2014

  • Cutler, Nick A.; Chaput, Dominique L.; Oliver, Anna E.
  • FEMS Microbiology Ecology, Vol. 91, Issue 3
  • DOI: 10.1093/femsec/fiu027

Killing by Type VI secretion drives genetic phase separation and correlates with increased cooperation
journal, February 2017

  • McNally, Luke; Bernardy, Eryn; Thomas, Jacob
  • Nature Communications, Vol. 8, Issue 1
  • DOI: 10.1038/ncomms14371

A standard protocol for describing individual-based and agent-based models
journal, September 2006


A Type VI Secretion-Related Pathway in Bacteroidetes Mediates Interbacterial Antagonism
journal, August 2014

  • Russell, Alistair B.; Wexler, Aaron G.; Harding, Brittany N.
  • Cell Host & Microbe, Vol. 16, Issue 2
  • DOI: 10.1016/j.chom.2014.07.007

High-throughput superhydrophobic microwell arrays for investigating multifactorial stem cell niches
journal, January 2016

  • Zhang, Pengfei; Zhang, Jianxiong; Bian, Shengtai
  • Lab on a Chip, Vol. 16, Issue 16
  • DOI: 10.1039/C6LC00331A

Understanding the sequential activation of Type III and Type VI Secretion Systems in Salmonella typhimurium using Boolean modeling
journal, January 2013

  • Das, Chandrani; Dutta, Anirban; Rajasingh, Hannah
  • Gut Pathogens, Vol. 5, Issue 1
  • DOI: 10.1186/1757-4749-5-28

Individual-based modelling of carbon and nitrogen dynamics in soils: Parameterization and sensitivity analysis of microbial components
journal, June 2011


Evaluation of a Yersinia pestis mutant impaired in a thermoregulated type VI-like secretion system in flea, macrophage and murine models
journal, November 2009


Modeling the effect of soil meso- and macropores topology on the biodegradation of a soluble carbon substrate
journal, September 2015


Spatial Organization of Microbial Biofilm Communities
journal, August 2000


A Type VI Secretion System of Pseudomonas aeruginosa Targets a Toxin to Bacteria
journal, January 2010


Human symbionts inject and neutralize antibacterial toxins to persist in the gut
journal, March 2016

  • Wexler, Aaron G.; Bao, Yiqiao; Whitney, John C.
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 13
  • DOI: 10.1073/pnas.1525637113

Assembly and Tracking of Microbial Community Development within a Microwell Array Platform
journal, January 2017

  • Timm, Andrea C.; Halsted, Michelle C.; Wilmoth, Jared L.
  • Journal of Visualized Experiments, Issue 124
  • DOI: 10.3791/55701

INDISIM-Paracoccus, an individual-based and thermodynamic model for a denitrifying bacterium
journal, August 2016


Established Microbial Colonies Can Survive Type VI Secretion Assault
journal, October 2015


Development of a simple static microwell array with uniform cell seeding and a chemical concentration gradient
journal, April 2017


Individual-based modelling of microbial activity to study mineralization of C and N and nitrification process in soil
journal, September 2005

  • Ginovart, Marta; López, Daniel; Gras, Anna
  • Nonlinear Analysis: Real World Applications, Vol. 6, Issue 4
  • DOI: 10.1016/j.nonrwa.2004.12.005

One-step fabrication of three-dimensional polydimethylsiloxane peel-off microwell array for cell trapping
journal, January 2015

  • Xue, Ning; Bleris, Leonidas; Lee, Jeong-Bong (JB)
  • Journal of Micro/Nanolithography, MEMS, and MOEMS, Vol. 14, Issue 1
  • DOI: 10.1117/1.JMM.14.1.014503

Tools for the Microbiome: Nano and Beyond
journal, December 2015


Development of transparent microwell arrays for optical monitoring and dissection of microbial communities
journal, November 2016

  • Halsted, Michelle; Wilmoth, Jared L.; Briggs, Paige A.
  • Journal of Vacuum Science & Technology B, Nanotechnology and Microelectronics: Materials, Processing, Measurement, and Phenomena, Vol. 34, Issue 6
  • DOI: 10.1116/1.4962739

Biofilms promote altruism
journal, August 2004


BacSim, a simulator for individual-based modelling of bacterial colony growth
journal, December 1998


INDISIM, An Individual-based Discrete Simulation Model to Study Bacterial Cultures
journal, January 2002

  • Ginovart, Marta; LÓPez, Daniel; Valls, Joaquim
  • Journal of Theoretical Biology, Vol. 214, Issue 2
  • DOI: 10.1006/jtbi.2001.2466

Stochastic Assembly of Bacteria in Microwell Arrays Reveals the Importance of Confinement in Community Development
journal, May 2016


Strain competition restricts colonization of an enteric pathogen and prevents colitis
journal, July 2016

  • Hecht, Aaron L.; Casterline, Benjamin W.; Earley, Zachary M.
  • EMBO reports, Vol. 17, Issue 9
  • DOI: 10.15252/embr.201642282

T6SS: The bacterial "fight club" in the host gut
journal, June 2017


Disentangling mechanisms that mediate the balance between stochastic and deterministic processes in microbial succession
journal, March 2015

  • Dini-Andreote, Francisco; Stegen, James C.; van Elsas, Jan Dirk
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 11
  • DOI: 10.1073/pnas.1414261112

Evolution of the CRISPR-Cas adaptive immunity systems in prokaryotes: models and observations on virus–host coevolution
journal, January 2015

  • Koonin, Eugene V.; Wolf, Yuri I.
  • Molecular BioSystems, Vol. 11, Issue 1
  • DOI: 10.1039/C4MB00438H

Soil microbial communities are shaped by plant-driven changes in resource availability during secondary succession
journal, December 2015


Quantitative single-cell characterization of bacterial interactions reveals type VI secretion is a double-edged sword
journal, November 2012

  • LeRoux, M.; De Leon, J. A.; Kuwada, N. J.
  • Proceedings of the National Academy of Sciences, Vol. 109, Issue 48
  • DOI: 10.1073/pnas.1213963109

Cell manipulation tool with combined microwell array and optical tweezers for cell isolation and deposition
journal, June 2013


The T6SSs of Pseudomonas aeruginosa Strain PAO1 and Their Effectors: Beyond Bacterial-Cell Targeting
journal, June 2016

  • Sana, Thibault G.; Berni, Benjamin; Bleves, Sophie
  • Frontiers in Cellular and Infection Microbiology, Vol. 6
  • DOI: 10.3389/fcimb.2016.00061

Structure of a Peptidoglycan Amidase Effector Targeted to Gram-Negative Bacteria by the Type VI Secretion System
journal, June 2012


Individual-Based Modeling of Carbon and Nitrogen Dynamics in Soils: Parameterization and Sensitivity Analysis of Abiotic Components
journal, January 2010


iDynoMiCS: next-generation individual-based modelling of biofilms: iDynoMiCS for Biofilm Modelling
journal, March 2011


Self-seeding microwell chip for the isolation and characterization of single cells
journal, January 2015

  • Swennenhuis, Joost F.; Tibbe, Arjan G. J.; Stevens, Michiel
  • Lab on a Chip, Vol. 15, Issue 14
  • DOI: 10.1039/C5LC00304K

The Landscape of Type VI Secretion across Human Gut Microbiomes Reveals Its Role in Community Composition
journal, September 2017


The ODD protocol: A review and first update
journal, November 2010


Works referencing / citing this record:

Disturbance Size Can Be Compensated for by Spatial Fragmentation in Soil Microbial Ecosystems
journal, August 2019

  • König, Sara; Köhnke, Merlin C.; Firle, Anouk-Letizia
  • Frontiers in Ecology and Evolution, Vol. 7
  • DOI: 10.3389/fevo.2019.00290

Modelización basada en agentes: canibalismo microbiano
journal, July 2019

  • Ginovart, Marta; Tutusaus, Albert; Mas, M. Teresa
  • Modelling in Science Education and Learning, Vol. 12, Issue 2
  • DOI: 10.4995/msel.2019.10975