sporeweb: an interactive journey through the complete sporulation

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  • SporeWeb: an interactive journey through thecomplete sporulation cycle of Bacillus subtilisRobyn T. Eijlander1,2,*, Anne de Jong1,2, Antonina O. Krawczyk1,2, Siger Holsappel2 and

    Oscar P. Kuipers2,*

    1Top Institute Food and Nutrition (TIFN), Nieuwe Kanaal 9A, 6709 PA Wageningen, The Netherlands and2Department of Molecular Genetics, Groningen Biomolecular Sciences and Biotechnology Institute,University of Groningen, 9747 AG Groningen, The Netherlands

    Received July 26, 2013; Revised and Accepted October 4, 2013

    ABSTRACT

    Bacterial spores are a continuous problem for bothfood-based and health-related industries. Decadesof scientific research dedicated towards under-standing molecular and gene regulatory aspects ofsporulation, spore germination and spore propertieshave resulted in a wealth of data and information.To facilitate obtaining a complete overview as wellas new insights concerning this complex and tightlyregulated process, we have developed a database-driven knowledge platform called SporeWeb (http://sporeweb.molgenrug.nl) that focuses on generegulatory networks during sporulation in theGram-positive bacterium Bacillus subtilis. Dynamicfeatures allow the user to navigate through allstages of sporulation with review-like descriptions,schematic overviews on transcriptional regulationand detailed information on all regulators and thegenes under their control. The Web site supportsdata acquisition on sporulation genes and theirexpression, regulon network interactions anddirect links to other knowledge platforms orrelevant literature. The information found onSporeWeb (including figures and tables) can andwill be updated as new information becomes avail-able in the literature. In this way, SporeWeb offersa novel, convenient and timely reference, an infor-mation source and a data acquisition tool that willaid in the general understanding of the dynamicsof the complete sporulation cycle.

    INTRODUCTION

    During adverse environmental conditions, bacterial cellsadopt developmental strategies, such as endospore

    formation, to ensure their survival. Bacterial spores area continuous problem in food- and health-relatedindustries because of their persistence after treatmentsand their ability to revert to vegetative cells through theprocess of germination (1,2). For instance, the disease ofanthrax can persevere through the ingestion of spores thatare able to survive the gastrointestinal tract and germinateto vegetative cells that produce lethal toxins (3). On theother hand, use of bacterial spores in the form ofbioinsecticides (4), antigen delivery systems and vaccines(5) or probiotics (6,7) are upcoming fields that offer at-tractive applications. Therefore, a better understanding ofthe sporulation and germination processes, the level ofheterogeneity therein, all genes and proteins involved, aswell as influential effects of environmental factors haveformed important fields of study for the past decades (8)and have provided a wealth of knowledge (912).Most of the work on sporulation has been performed

    using the Gram-positive non-pathogenic organismBacillus subtilis. The obtained data are extremelyvaluable and are often used as a reference model in sporu-lation research concerning other (pathogenic) bacteria,including Bacillus anthracis (13,14), Bacillus cereus(15,16) and various Clostridium species and strains thatare of both medical and industrial importance (includingClostridium difficile, Clostridium perfringens andClostridium botulinum) (1722). This results in even moredata and information, with various theories and specula-tions on molecular mechanisms, conservation of coresporulation genes and emergence of evolutionary founda-tions (23,24). Sporulation of B. subtilis is an extremelycomplex cellular developmental process (11,25,26).New technological advances such as RNA sequencing,identification of small non-coding RNAs and increasedunderstanding of processes through mathematicalmodelling allow us to answer questions beyond previousexpectations (2731), but simultaneously add to thecomplexity. Newly sequenced bacterial genomes of other

    *To whom correspondence should be addressed. Tel: +31 50 3632190; Fax: +31 50 363 2348; Email: R.T.Eijlander@rug.nlCorrespondence may also be addressed to Oscar P. Kuipers. Tel: +31 50 3632093; Fax: +31 50 363 2348; Email: O.P.Kuipers@rug.nl

    Published online 28 October 2013 Nucleic Acids Research, 2014, Vol. 42, Database issue D685D691doi:10.1093/nar/gkt1007

    The Author(s) 2013. Published by Oxford University Press.This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercialre-use, please contact journals.permissions@oup.com

    Downloaded from https://academic.oup.com/nar/article-abstract/42/D1/D685/1041414by gueston 17 February 2018

    http://sporeweb.molgenrug.nlhttp://sporeweb.molgenrug.nlaverse,due to backutilization vaccins,isisC.C.C.",0,0,2",0,0,2 emerging's

  • spore-formers are increasingly available due to faster andcheaper methodologies and demand efficient analyses andreadily available databases for comparison purposes (32).Therefore, a general overview on how spore formation isestablished (including which genes and regulatorypathways are involved) is very valuable to the field, butdue to the complexity and dynamics increasingly difficultto obtain.In this work, we describe a novel knowledge and data

    acquisition platform called SporeWeb (http://sporeweb.molgenrug.nl), which focuses on all developmental stagesof sporulation of B. subtilis from a gene regulatory pointof view. Through an interactive web interface querying theSporeWeb database (details available in SupplementaryMaterial), it offers both a textual description and a graph-ical representation of the sequence of events throughoutspore development (Figure 1). Importantly, it easily linksto more catalogued information present on other know-ledge Web sites, such as SubtiWiki (http://subtiwiki.uni-goettingen.de/) (33). This allows the reader to grasp whathappens inside the cell on the regulatory level, with add-itional detailed information on key regulatory proteinsinvolved. The database-driven SporeWeb Web site isdynamic and will be updated and extended when novelscientific data become available in the future. We believethat SporeWeb will be a continuous valuable asset to theresearch field of bacterial sporulation and will aid in our

    overall understanding of this complex developmentalprocess.

    An interactive journey through all stages of the bacterialsporulation process

    Commitment to sporulation is characterized by asymmet-ric cell division and expression of dedicated gene sets (34).This expression is tightly regulated in various sequentialdevelopmental stages and governed by complex biochem-ical communication between the two compartments of thecell (11). SporeWeb offers an interactive review of thiscomplete process, which is the result of an extensive lit-erature study. The homepage serves as a starting point forany sporulation stage of interest, which can be accessed byclicking on the homepage image or by selecting the Statein the menu bar. Subsequent pages offer both detaileddescriptions and schematic representations of develop-ment. The figures are interactive and dynamic: theycontain clickable items of interest and ensure updated in-formation as genes are added to or edited in the database.Legends to the figures are described in the vertical grey baron the right of the web page, whereas a review-likedescription of the sporulation state is shown below thefigure, with direct links to relevant literature references.

    Sporulation-specific regulators and their regulons aredescribed on individual pages, which can be accessed by

    Figure 1. Graphical representation of the different levels in the SporeWeb Web site.

    D686 Nucleic Acids Research, 2014, Vol. 42, Database issue

    Downloaded from https://academic.oup.com/nar/article-abstract/42/D1/D685/1041414by gueston 17 February 2018

    ,http://sporeweb.molgenrug.nlhttp://sporeweb.molgenrug.nlfocusseshttp://nar.oxfordjournals.org/lookup/suppl/doi:10.1093/nar/gkt1007/-/DC1http://nar.oxfordjournals.org/lookup/suppl/doi:10.1093/nar/gkt1007/-/DC1whttp://subtiwiki.uni-goettingen.de/http://subtiwiki.uni-goettingen.de/wbecomes'' side

  • clicking on the item in the schematic figures or via themenu bar. An example of such a page is shown inFigure 2. Genes under transcriptional control of aspecific regulator have been indicated in blue or redboxes for transcriptional activation or repression, respect-ively. Additionally, there is a direct link to the SubtiWikilist of regulon members. Lists and descriptions of all geneswithin the regulon can be downloaded in the form of up-datable Excel sheets by clicking on the coloured boxes orvia the Excel icon in the top right corner (Figure 2).

    Graphic representations of regulon interactions definesubgroups of co-regulated genes

    As sporulation progresses, sporulation-specific sigmafactors are expressed and activated in a spatial andtemporal manner (11,26). Together with secondary regu-lator proteins, they control the timing, sequence and levelof gene expression that are necessary for formation,maturation and release of the endospore. Varioustranscriptomic studies in B. subtilis have led to the identi-fication of genes controlled by these sigma factors and

    other regulators to map the sporulation gene regulatorynetworks (3542). In SporeWeb, we have visualizedthese networks using Cytoscape-generated layouts forevery sporulation-specific stage (details available inSupplementary Material) (43). These layouts can beaccessed via the Cytoscape o

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