MODELING THE METABOLISM AND EVOLUTION OF BACTERIA IN THE SHEWANELLA GENUS

• Sponsoring Institution: National Institute of Food and Agriculture
• Project Status: TERMINATED
• Funding Source: HATCH
• Reporting Frequency: Annual
• Accession No.: 1007170
• Project No.: RI0015-H002
• Project Start Date: Aug 10, 2015
• Project End Date: Sep 30, 2019

Project Director
Zhang, YI.

Recipient Organization
UNIVERSITY OF RHODE ISLAND
19 WOODWARD HALL 9 EAST ALUMNI AVENUE
KINGSTON,RI 02881

Performing Department
Cell and Molecular Biology

Non Technical Summary
Shewanella is a diverse group of microorganisms that widely occur in soil and water, and are often associated with the spoilage of meat and milk products. It is not clear how this group evolves and what leads to the emergence of pathogenicity. Using computational modeling, in this project we will simulate the evolution and metabolic diversity of Shewanella. Through this project, we expect to develop new methods for the detection and prevention of Shewanella contaminants in meat and agricultural products.

Animal Health Component

0%

Research Effort Categories

Basic

100%

Applied

(N/A)

Developmental

(N/A)

Classification

Knowledge Area (KA)	Subject of Investigation (SOI)	Field of Science (FOS)	Percent
711	5010	1103	100%

Knowledge Area
711 - Ensure Food Products Free of Harmful Chemicals, Including Residues from Agricultural and Other Sources;

Subject Of Investigation
5010 - Food;

Field Of Science
1103 - Other microbiology;

Keywords

shewanella

food contaminants

environmental remediation

Goals / Objectives
The overarching goal of the proposed project is to construct genome-scale models of the metabolism and evolution of Shewanella species, which are widely distributed in soil and water, and are often associated with the spoilage of meat and milk products. The integrated modeling will facilitate the development of new genetic markers for the more accurate detection of Shewanella contaminations, and it will provide insights into the prevention of food spoilage. Additionally, Shewanella species have significant applications in biogeochemical cycling in the coastal environment. Its potential associations with marine animals can also influence the quality and quantity of ecologically and economically important agricultural species. Furthermore, the computational tools developed from this project can be applied to study other species of significant environmental influences.

Project Methods
This research will combine comparative genomics with metabolic modeling, which are two widely used methods that have not yet been fully integrated in studying microorganisms. The modeling results will be analyzed using software that is being developed in our laboratory, and will be evaluated based on existing experimental results in current literature.

Progress 08/10/15 to 09/30/19

Outputs
Target Audience: Graduate students, attendence of invited seminar and scientific conferences, readers of our publication in peer-reviewed journals and invited book chapter. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Over the past five years, the funded project has provided opportunities for training three undergraduate students, six graduate students, and two postdoctoral fellows in the interdisciplinary area of Computational Biology. How have the results been disseminated to communities of interest?An open-source software has been initiated through initial start-up funding of the project. Four peer-reviewed manuscripts and an invited book chapter has been published with support from this grant. Additionally, six peer-reviewed journal publications, eight invited seminars, and over 20 conference presentations have been presented by the PI and the trainees in her laboratory. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Over the past five years, the funded project has provided opportunities for training three undergraduate students, six graduate students, and two postdoctoral fellows in the interdisciplinary area of Computational Biology. An open-source software has been initiated through initial start-up funding of the project. Four peer-reviewed manuscripts and an invited book chapter has been published with support from this grant. Additionally, six peer-reviewed journal publications, eight invited seminars, and over 20 conference presentations have been presented by the PI and the trainees in her laboratory. The funded research also provided an opportunity for the PI, an early career faculty, to broaden her research directions. Besides meeting the goals in studying the metabolic mechanisms in the bacterial genus Shewanella, the PI's lab has opened new research programs into studying the microbiome of eastern oyster, a commercially important aquaculture species in Rhode Island. Our research findings, together with the student training and workforce development, provided new opportunities that would furthering the goals of the land grant.

Publications

• Type: Journal Articles Status: Published Year Published: 2019 Citation: Williams LE, Cullen N, DeGiorgis JA, Martinez KJ, Mellone J, Oser M, Wang J, Zhang Y. (2019) Variation in genome content and predatory phenotypes between Bdellovibrio sp. NC01 isolated from soil and B. bacteriovorus type strain HD100. Microbiology. doi: 10.1099/mic.0.000861.
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Fernandez Robledo JA, Yadavalli R, Allam B, Pales Espinosa E, Gerdol M, Greco S, Gomez-Chiarri M, Stevick RJ, Zhang Y, Heil C, Bishop-Bailey D, Metzger MJ. (2019) From the raw bar to the bench: Bivalves as models for human health. Developmental and Comparative Immunology 92, 260282. doi:10.1016/j.dci.2018.11.020.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Pimentel ZT and Zhang Y. (2018) Evolution of the natural transformation protein, ComEC, in Bacteria. Frontiers in Microbiology 9:2980. doi:10.3389/fmicb.2018.02980.
• Type: Conference Papers and Presentations Status: Published Year Published: 2019 Citation: Pimentel Z, Cres C, Smolowitz R, Gomez-Chiarri M, Zhang Y. Boston Bacterial Meeting, Taxonomic and functional profiling of the microbiome of the eastern oyster, Crassostrea virginica. Boston, MA, June 2019. (Poster)

Progress 10/01/17 to 09/30/18

Outputs
Target Audience:Graduate students, attendence of invited seminar and scientific conferences, readers of our publication in peer-reviewed journal and invited book chapter. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?Training opportunities were provided to four graduate students and four undergraduate students. Two students are co-authors on peer-reviewed publications. All students are trained in the interdisciplinary field of computational biology. How have the results been disseminated to communities of interest? The research outcomes were disseminated through journal publication, invited seminars, and conference presentations by the PI and her students. § indicates trainees from my group, and * indicates work led by my group. Publications: Fernandez Robledo JA, Yadavalli R, Allam B, Pales Espinosa E, Gerdol M, Greco S, Gomez-Chiarri M, Stevick RJ, Zhang Y, Heil C, Bishop-Bailey D, Metzger MJ. (2019) From the raw bar to the bench: Bivalves as models for human health. Developmental and Comparative Immunology 92, 260-282. doi:10.1016/j.dci.2018.11.020. * Pimentel ZT§ and Zhang Y. (2018) Evolution of the natural transformation protein, ComEC, in Bacteria. Frontiers in Microbiology 9:2980. doi:10.3389/fmicb.2018.02980. Mokszycki ME, Leatham-Jensen M, Steffensen JL, Zhang Y, Krogfelt KA, Caldwell ME, Conway T, and Cohen PS. (2018) A Simple In Vitro Gut Model for Studying the Interaction between Escherichia coli and the Intestinal Commensal Microbiota in Cecal Mucus. Applied and Environmental Microbiology. doi:10.1128/AEM.02166-18. Waite DW, Vanwonterghem I, Rinke C, Parks DH, Zhang Y, Takai K, Sievert SM, Simon J, Campbell BJ, Hanson TE, Woyke T, Klotz MG and Hugenholtz P. (2018) Addendum: Comparative Genomic Analysis of the Class Epsilonproteobacteria and Proposed Reclassification to Epsilonbacteraeota (phyl. nov.). Frontiers in Microbiology 9:772. doi: 10.3389/fmicb.2018.00772 * Steffensen JL§, Dufault-Thompson K§, Zhang Y. (2018) FindPrimaryPairs: An efficient algorithm for predicting element-transferring reactant/product pairs in metabolic networks. PLoS ONE 13(2): e0192891. Presentations: Zhang Y. University of Massachusetts Amherst, Microbiology Department, "Genome-scale models: from marine microbes to host-microbe associations." Amherst, MA, May 2018. Zhang Y. International Aphid Genomics Consortium workshop, Entomological Society of America Annual Conference, "Reconstructing the metabolism and evolution of Daktulosphaira vitifoliae from genome sequences." Denver, CO, November 2017. * Paulson S§, Pimentel ZT§, Zhang Y. Students' Seminar, Summer Undergraduate Research Fellowship in Oceanography, "Microbial Community Profiling of Eastern Oysters (Crassostrea virginica) Infected with Perkinsus marinus." Narragansett, RI, August 2018. (Oral presentation) * Pepin M§, Zhao W§, Zhang Y. RI SURF Conference, "Genome-Scale Metabolic Model for Haemophilus parainflenzae." Kingston, RI, July 2018. (Poster) * Baranowski E§, Zhao W§, Zhang Y. RI SURF Conference, "A Genomic­Scale Metabolic Model of Pyrococcus furiosus, strain DSM 3638." Kingston, RI, July 2018. (Poster) * Zhang Y, Steffensen J§, Dufault-Thompson K§, Zhang K§. Function-SIG, Intelligent Systems for Molecular Biology (ISMB), "Visualization and annotation of genome-scale metabolic networks." Chicago, IL, July 2018. (Competitive talk selected from abstract submissions) * Dufault-Thompson K§ and Zhang Y. Ocean Carbon Biogeochemistry, summer workshop, "Simulating marine microbial metabolism using genome scale models." Woods Hole, MA, June 2018. (Poster) * Dufault-Thompson K§ and Zhang Y. RI NSF CAIM Symposium, "Developing genome scale models for the simulation of microbial metabolism." Kingston, RI, April 2018. (Poster) * Pimentel ZT§ and Zhang Y. RI NSF CAIM Symposium, "Diversity and Evolution of the Natural Transformation Protein ComEC." Kingston, RI, April 2018. (Poster) What do you plan to do during the next reporting period to accomplish the goals? We will continue carrying out the aims of this project through implementing advanced modeling tools for microbial metabolism and evolutionary analysis. We will also seek the broad application of our tools into study the metabolism and control of other relevant species in agriculture, e.g. insect pests.

Impacts
What was accomplished under these goals? During the past year, we focused on developing computational technologies into analyzing the metabolism and genomic evolution of Shewanella and extending the application of our tools into analyzing species from all three domains of life. Some of the new organisms we analyzed included the aphid insect, which is a pest species for crops in agricultural production. By applying our newly developed technology to aphids, we aim to understand key molecular pathways for intervening with aphid metabolism and potentially leading to new pest control approaches. We have also performed a global evolutionary analysis of all bacteria on a protein called ComEC that contributes to the acquisition of novel genes and functions among diverse bacteria. This would lead to a better understanding of the evolution of metabolic activities.

Publications

• Type: Journal Articles Status: Published Year Published: 2018 Citation: Steffensen JL, Dufault-Thompson K, Zhang Y. (2018) FindPrimaryPairs: An efficient algorithm for predicting element-transferring reactant/product pairs in metabolic networks. PLoS ONE 13(2): e0192891.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Pimentel ZT and Zhang Y. (2018) Evolution of the natural transformation protein, ComEC, in Bacteria. Frontiers in Microbiology 9:2980. doi:10.3389/fmicb.2018.02980.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Mokszycki ME, Leatham-Jensen M, Steffensen JL, Zhang Y, Krogfelt KA, Caldwell ME, Conway T, and Cohen PS. (2018) A Simple In Vitro Gut Model for Studying the Interaction between Escherichia coli and the Intestinal Commensal Microbiota in Cecal Mucus. Applied and Environmental Microbiology. doi:10.1128/AEM.02166-18.
• Type: Journal Articles Status: Published Year Published: 2019 Citation: Fernandez Robledo JA, Yadavalli R, Allam B, Pales Espinosa E, Gerdol M, Greco S, Gomez-Chiarri M, Stevick RJ, Zhang Y, Heil C, Bishop-Bailey D, Metzger MJ. (2019) From the raw bar to the bench: Bivalves as models for human health. Developmental and Comparative Immunology 92, 260282. doi:10.1016/j.dci.2018.11.020.
• Type: Journal Articles Status: Published Year Published: 2018 Citation: Waite DW, Vanwonterghem I, Rinke C, Parks DH, Zhang Y, Takai K, Sievert SM, Simon J, Campbell BJ, Hanson TE, Woyke T, Klotz MG and Hugenholtz P. (2018) Addendum: Comparative Genomic Analysis of the Class Epsilonproteobacteria and Proposed Reclassification to Epsilonbacteraeota (phyl. nov.). Frontiers in Microbiology 9:772. doi: 10.3389/fmicb.2018.00772

Progress 10/01/16 to 09/30/17

Outputs
Target Audience: Graduate students, attendence of invited seminar and scientific conferences, readers of our publication in peer-reviewed journal and invited book chapter. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project supports the training of a third-year graduate student, who has so far co-authored two peer-reviewed publications and an invited book chapter. A second graduate student was also trained with materials generated from the project and is applying the computational skills into studying host-associated microbial communities. How have the results been disseminated to communities of interest?The research outcomes were disseminated through journal publication and conference presentations by the PI and her students: Publications: Dufault-Thompson K§, Jian H, Cheng R, Li J, Wang F, and Zhang Y*. (2017) A Genome-Scale Model of Shewanella piezotolerans Simulates Mechanisms of Metabolic Diversity and Energy Conservation. mSystems (ASM), 2, e00165-16. Dufault-Thompson K, Steffensen JL, Zhang Y (2018) Using PSAMM for the Curation and Analysis of Genome-Scale Metabolic Models. In: Fondi M, editor. Metabolic Network Reconstruction and Modeling: Methods and Protocols. New York, NY: Springer New York. pp. 131-150. doi:10.1007/978-1-4939-7528-0_6. Presentations: Zhang Y. Invited Seminar, MIT Microbial Systems Seminar, "Simulating the metabolism and evolution of microbial systems using genome-scale models." Boston, MA, May 2017. Dufault-Thompson K§, Wilson A, Zhang Y*. Gordon Research Conference, Animal-Microbe Symbioses, "Genome-scale models: simulating the metabolism and evolution of obligate endosymbiosis." West Dover, VT, June 2017. (Poster) Stevick RJ§, Pimentel Z§, Post AF, Zhang Y, Go?mez-Chiarri M. Gordon Research Conference, Animal-Microbe Symbioses, "Probiotic-driven changes in the rearing water microbial community in an oyster hatchery." West Dover, VT, June 2017. (Poster) Flasco M¶, Pimentel Z§, Gregory S, Zhang Y*. Students' Seminar, Summer Undergraduate Research Fellowship in Oceanography, "Exploring the relationship between genetic variance in ComEC and uptake efficiency in natural transformation." Narragansett, RI, August 2017. (Oral presentation) Lord A¶, Dufault-Thompson K, Zhang Y*. RI SURF Conference, "Exploring the relationship between genetic variance in ComEC and uptake efficiency in natural transformation." Kingston, RI, July 2017. (Poster) Kopac S, Pimentel Z§, Gregory S, Zhang Y*. RI NSF EPSCoR Research Symposium, "Investigating functional roles of the comEC gene variants on bacterial natural transformation." Providence, RI, April 2017. (Poster) Dufault-Thompson K§, Jian H, Cheng R, Li J, Wang F, Zhang Y*. RI NSF EPSCoR Research Symposium, "Investigating Energy Metabolism and Metabolic Diversity using a Genome-Scale Model of Shewanella piezotolerans." Providence, RI, April 2017. (Poster) Stevick RJ§, Modak T§, Pimentel Z§, Zhang Y, Post AF, Gomez-Chiarri M. National Shellfisheries Association Annual Meeting, "Probiotic-driven changes in rearing water microbial community structure and function in an oyster hatchery." Knoxville, TN, March 2017. (Poster) What do you plan to do during the next reporting period to accomplish the goals?We will continue carrying out the aims of this project through implementing advanced modeling tools for microbial metabolism and evolutionary analysis. We are currently working with our collaborators to generate new experimental data to evaluate and advance our modeling protocols.

Impacts
What was accomplished under these goals? In the past year, we have focused on applying our modeling software to simulate the anaerobic carbon metabolism of a cold-tolerating Shewanella species. This study was published in the ASM journal mSystems, and a graduate student was trained in this research. We have also published a book chapter inthe new book titled "Metabolic Network Reconstruction and Modeling" in the "Methods in Molecular Biology" book series (MIMB, volume 1716). A new manuscript has also been developed on a new algorithm for analyzing metabolic networks and is currently under review.

Publications

• Type: Journal Articles Status: Published Year Published: 2017 Citation: Dufault-Thompson K, Jian H, Cheng R, Li J, Wang F, and Zhang Y. (2017) A Genome-Scale Model of Shewanella piezotolerans Simulates Mechanisms of Metabolic Diversity and Energy Conservation. mSystems (ASM), 2, e00165-16.
• Type: Journal Articles Status: Under Review Year Published: 2017 Citation: Steffensen JL and Zhang Y. (2017) FindPrimaryPairs: An efficient algorithm for predicting element-transferring reactant/product pairs in metabolic networks. (Under Review)
• Type: Book Chapters Status: Published Year Published: 2018 Citation: Dufault-Thompson K, Steffensen JL, Zhang Y (2018) Using PSAMM for the Curation and Analysis of Genome-Scale Metabolic Models. In: Fondi M, editor. Metabolic Network Reconstruction and Modeling: Methods and Protocols. New York, NY: Springer New York. pp. 131150. doi:10.1007/978-1-4939-7528-0_6.

Progress 10/01/15 to 09/30/16

Outputs
Target Audience:Undergraduate students and trainees, graduate students, attendence of scientific conferences including theInternational Symposium on Microbial Ecology,Intelligent Systems for Molecular Biology, and theOcean Science Meeting, readers of our publication in the journal PLoS Computational Biology. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This project supports the training of a second-year PhD student, an undergraduate student during the academic year, and twosummer undergraduate research students. Students learn the basic skills of genome annotation, metabolic modeling, and developed new programs for carrying out specific modeling tasks. How have the results been disseminated to communities of interest?The research outcomes were disseminated through journal publication and conference presentations by the PI and the graduate student: Publication: Steffensen JL, Dufault-Thompson K, Zhang Y. PSAMM: A Portable System for the Analysis of Metabolic Models. PLOS Comput Biol. Public Library of Science; 2016;12: e1004732. doi:10.1371/journal.pcbi.1004732; Conference presentations: (1) Steffensen J, Dufault-Thompson K, Zhang Y. International Symposium on Microbial Ecology (ISME), "Portable System for the Analysis of Metabolic Models (PSAMM): linking -omics data into genome-scale models." Montreal, Canada, August 2016. (Poster); (2) Zhang Y, Dufault-Thompson K, Steffensen J. Highlights Track, Intelligent Systems for Molecular Biology (ISMB), "PSAMM: A Portable System for the Analysis of Metabolic Models." Orlando, FL, July 2016. (Competitive talk selected from abstract submissions); (3) Zhang Y. International Society for Computational Biology, Function SIG, "Using PSAMM for integrating functional annotations into phenotypic simulations." Orlando, FL, July 2016. (Competitive talk selected from abstract submissions); (4) Dufault-Thompson K, Steffensen J, Zhang Y. Ocean Science Meeting, "Building Single-Cell Models of Planktonic Metabolism Using PSAMM." New Orleans, LA, February 2016. (Poster) What do you plan to do during the next reporting period to accomplish the goals?We will continue carrying out the aims of this project through modelconstruction and computational tool development. A manuscript that report our first model of a novel taxonomic branch in the Shewanella genus is being revised, and we will continue this effort and further apply our model into understanding the metabolism and evolution of Shewanella.

Impacts
What was accomplished under these goals? In the past year, we have mainly focused on three tasks: (1) metabolic modeling and software development; (2) Phylogenetic reconstruction and evaluation of gene essentiality; (3) model construction of a cold-tolerant Shewanella species. A third-year graduate student and a number of summer undergraduate students has been trained through this project. The graduate student has submitted a first-author manuscript on his research outcomes and is currently revising the manuscript based on reviewers' comments.

Publications

• Type: Journal Articles Status: Published Year Published: 2016 Citation: Steffensen JL, Dufault-Thompson K, Zhang Y. PSAMM: A Portable System for the Analysis of Metabolic Models. PLOS Comput Biol. Public Library of Science; 2016;12: e1004732. doi:10.1371/journal.pcbi.1004732

Progress 08/10/15 to 09/30/15

Outputs
Target Audience:During this reporting period, we have initiated the training of a graduate student in the interdisciplinary area of computational biology. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided?This reporting period has support one-month training of a first-year graduate student in the interdisciplinary field of computational biology. How have the results been disseminated to communities of interest?The initial development of our new softwarehas been disseminated to the scientific community through the public sharing of a software repositoryhttps://zhanglab.github.io/psamm/. What do you plan to do during the next reporting period to accomplish the goals?In the next reporting period, we plan to disseminate our findings from the development of genome-scale modeling tools into a journal publication. We will work towards the objective of specific aim 1 to identify genomic traits that involved in the regulation of contaminant phenotypes.

Impacts
What was accomplished under these goals? Thisreporting period has covered the first month of our proposed project, so much of the effort has been focused on the training of graduate students and the construction of genome-scale modeling tools. Through this initial set up, a student has been trained and is ready to perform research towards the proposed goals, and we have initiated a computational software that can be applied for the analysis of genome-scale models.

Publications