1471-2105-13-S12-A10
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MEETING ABSTRACT Open Access Identifying indispensable proteins of the type III secretion systems of Salmonella enterica serovar Typhimurium strain LT2 Chandrajit Lahiri 1,2* , Pawar Shrikant 3,4 , Radhakrishnan Sabarinathan 5 , M Izhar Ashraf 6 , Dipshikha Chakravortty 1 From 11th Annual UT-ORNL-KBRIN Bioinformatics Summit 2012 Louisville, KY, USA. 30 March - 1 April 2012 Background An estimated 1.3 billion cases of salmonellosis occur worldwide every year [1]. The causative organism Salmo- nella enterica serovar Typhimurium strain LT2 uses dif- ferent proteins to inject into the host cells to cause such systemic infection. Several reports exist on the role and importance of these individual proteins of the Type III secretion system of Salmonella pathogenicity islands (SPI). Two component signal transduction system plays a major role in regulation of those virulent SPI genes [2]. However, the most indispensable of them and their hierarchical role has not been worked out in detail. Materials and methods We have adopted a graph theoretical approach to build a network of these and other associated signal transduction proteins and utilized modules like centrality measures and network decomposition to analyze our result. An initial approach to get the fingerprint of the network via k-core analyses listed out the set of proteins InvA, InvE, InvG, InvF, PrgK, SicA, SipA, SipB, SipC, SpaK, SpaL, SpaO, SpaP, SpaQ, SpaR, SpaS, SsaJ, SsaK, SsaL, SsaM, SsaN, SsaO, SsaP, SsaQ, SsaS, SsaT, SsaU, SsaV, and YscR which comes into action in the process of invasion and coloniza- tion and thus become indispensable than the rest. All the significant proteins identified were confirmed by Agilent Microarray with subsequent Cytoscape analysis. Results The chaperone protein SicA was figured out to be the most indispensable one from classical centrality measures and confirmed by microarray analyses as well. We also propose a hierarchy of the proteins involved in the total infection process. Our method is the first of its kind to figure out, albeit theoretically, potential virulence deter- minants encoded by SPI for therapeutic targets for enteric infection. Conclusions Target genes were identified and then validated by using independent, published microarray data. The result is a targeted set of genes that are sensitive predictors which could then form the basis for a series of tests in the wet-lab background. Understanding these regulatory and virulent genes will provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection which will further contri- bute in identifying new targets for antimicrobial agents. Author details 1 Center for Infectious Diseases Research, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India. 2 Department of Bioinformatics, School of Biotechnology and Health Sciences, Karunya University, Coimbatore 641114, India. 3 Department of Biology, Western Kentucky University, Bowling Green, Kentucky 42101, USA. 4 Department of Cell and Developmental Biology, Cornell University, Weill Cornell Medical College, Manhattan, NY 10065, USA. 5 Bioinformatics Center, Indian Institute of Science, Bangalore - 560012, India. 6 Theoretical Physics, The Institute of Mathematical Sciences, Chennai - 600113, India. Published: 31 July 2012 References 1. Coburn B, Grassl GA, Finlay BB: Salmonella, the host and disease: a brief review. Immunol Cell Biol 2007, 85:112-118. 2. Dziejman M, Mekalanos J: Two-component signal transduction and its role in the expression of bacterial virulence factors. In Two-component signal transduction. ASM Press, Washington, DC;Hoch JA, Silhavy TJ 1995:305-318. * Correspondence: [email protected] 1 Center for Infectious Diseases Research, Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India Full list of author information is available at the end of the article Lahiri et al. BMC Bioinformatics 2012, 13(Suppl 12):A10 http://www.biomedcentral.com/1471-2105/13/S12/A10 © 2012 Lahiri et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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MEETING ABSTRACT Open Access
Identifying indispensable proteins of the type IIIsecretion systems of Salmonella enterica serovarTyphimurium strain LT2Chandrajit Lahiri1,2*, Pawar Shrikant3,4, Radhakrishnan Sabarinathan5, M Izhar Ashraf6, Dipshikha Chakravortty1
From 11th Annual UT-ORNL-KBRIN Bioinformatics Summit 2012Louisville, KY, USA. 30 March - 1 April 2012
BackgroundAn estimated 1.3 billion cases of salmonellosis occurworldwide every year [1]. The causative organism Salmo-nella enterica serovar Typhimurium strain LT2 uses dif-ferent proteins to inject into the host cells to cause suchsystemic infection. Several reports exist on the role andimportance of these individual proteins of the Type IIIsecretion system of Salmonella pathogenicity islands (SPI).Two component signal transduction system plays a majorrole in regulation of those virulent SPI genes [2]. However,the most indispensable of them and their hierarchical rolehas not been worked out in detail.
Materials and methodsWe have adopted a graph theoretical approach to build anetwork of these and other associated signal transductionproteins and utilized modules like centrality measures andnetwork decomposition to analyze our result. An initialapproach to get the fingerprint of the network via k-coreanalyses listed out the set of proteins InvA, InvE, InvG,InvF, PrgK, SicA, SipA, SipB, SipC, SpaK, SpaL, SpaO,SpaP, SpaQ, SpaR, SpaS, SsaJ, SsaK, SsaL, SsaM, SsaN,SsaO, SsaP, SsaQ, SsaS, SsaT, SsaU, SsaV, and YscR whichcomes into action in the process of invasion and coloniza-tion and thus become indispensable than the rest. All thesignificant proteins identified were confirmed by AgilentMicroarray with subsequent Cytoscape analysis.
ResultsThe chaperone protein SicA was figured out to be themost indispensable one from classical centrality measures
and confirmed by microarray analyses as well. We alsopropose a hierarchy of the proteins involved in the totalinfection process. Our method is the first of its kind tofigure out, albeit theoretically, potential virulence deter-minants encoded by SPI for therapeutic targets forenteric infection.
ConclusionsTarget genes were identified and then validated by usingindependent, published microarray data. The result is atargeted set of genes that are sensitive predictors whichcould then form the basis for a series of tests in thewet-lab background. Understanding these regulatory andvirulent genes will provide insight into conditions whichare encountered by this intracellular enteric pathogenduring the course of infection which will further contri-bute in identifying new targets for antimicrobial agents.
Author details1Center for Infectious Diseases Research, Department of Microbiology andCell Biology, Indian Institute of Science, Bangalore 560012, India.2Department of Bioinformatics, School of Biotechnology and HealthSciences, Karunya University, Coimbatore 641114, India. 3Department ofBiology, Western Kentucky University, Bowling Green, Kentucky 42101, USA.4Department of Cell and Developmental Biology, Cornell University, WeillCornell Medical College, Manhattan, NY 10065, USA. 5Bioinformatics Center,Indian Institute of Science, Bangalore - 560012, India. 6Theoretical Physics,The Institute of Mathematical Sciences, Chennai - 600113, India.
Published: 31 July 2012
References1. Coburn B, Grassl GA, Finlay BB: Salmonella, the host and disease: a brief
review. Immunol Cell Biol 2007, 85:112-118.2. Dziejman M, Mekalanos J: Two-component signal transduction and its
role in the expression of bacterial virulence factors. In Two-componentsignal transduction. ASM Press, Washington, DC;Hoch JA, Silhavy TJ1995:305-318.
* Correspondence: [email protected] for Infectious Diseases Research, Department of Microbiology andCell Biology, Indian Institute of Science, Bangalore 560012, IndiaFull list of author information is available at the end of the article
Lahiri et al. BMC Bioinformatics 2012, 13(Suppl 12):A10http://www.biomedcentral.com/1471-2105/13/S12/A10
© 2012 Lahiri et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative CommonsAttribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction inany medium, provided the original work is properly cited.
doi:10.1186/1471-2105-13-S12-A10Cite this article as: Lahiri et al.: Identifying indispensable proteins of thetype III secretion systems of Salmonella enterica serovar Typhimuriumstrain LT2. BMC Bioinformatics 2012 13(Suppl 12):A10.
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