title: Interactome analyses of Salmonella pathogenicity islands reveal SicA indispensable for virulence.
abstract: BACKGROUND
  Serovars of Salmonella enterica, namely Typhi and Typhimurium, reportedly, are the bacterial pathogens causing systemic infections like gastroenteritis and typhoid fever. To elucidate the role and importance in such infection, the proteins of the Type III secretion system of Salmonella pathogenicity islands and two component signal transduction systems, have been mainly focused. However, the most indispensable of these virulent ones and their hierarchical role has not yet been studied extensively.
  
  
  RESULTS
  We have adopted a theoretical approach to build an interactome comprising the proteins from the Salmonella pathogeneicity islands (SPI) and two component signal transduction systems. This interactome was then analyzed by using network parameters like centrality and k-core measures. An initial step to capture the fingerprint of the core network resulted in a set of proteins which are involved in the process of invasion and colonization, thereby becoming more important in the process of infection. These proteins pertained to the Inv, Org, Prg, Sip, Spa, Ssa and Sse operons along with chaperone protein SicA. Amongst them, SicA was figured out to be the most indispensable protein from different network parametric analyses. Subsequently, the gene expression levels of all these theoretically identified important proteins were confirmed by microarray data analysis. Finally, we have proposed a hierarchy of the proteins involved in the total infection process. This theoretical approach is the first of its kind to figure out potential virulence determinants encoded by SPI for therapeutic targets for enteric infection.
  
  
  CONCLUSIONS
  A set of responsible virulent proteins was identified and the expression level of their genes was validated by using independent, published microarray data. The result was a targeted set of proteins that could serve as sensitive predictors and form the foundation for a series of trials in the wet-lab setting. Understanding these regulatory and virulent proteins would provide insight into conditions which are encountered by this intracellular enteric pathogen during the course of infection. This would further contribute in identifying novel targets for antimicrobial agents.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India. Electronic address: chandrajit@imsc.res.in.
authors.forename: Chandrajit
authors.initials: C
authors.lastname: Lahiri
authors.affiliation: Department of Biology, Georgia State University, Atlanta, GA 30303, USA. Electronic address: spawar2@gsu.edu.
authors.forename: Shrikant
authors.initials: S
authors.lastname: Pawar
authors.affiliation: Bioinformatics Center, Indian Institute of Science, Bangalore 560012, India. Electronic address: sabari.iisc@gmail.com.
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Sabarinathan
authors.affiliation: B.S. Abdur Rahman University, Vandalur, Chennai 600048, India. Electronic address: ashraf@imsc.res.in.
authors.forename: Md Izhar
authors.initials: MI
authors.lastname: Ashraf
authors.affiliation: Department of Bioinformatics, Karunya University, Coimbatore 641114, India. Electronic address: yaminichand@karunya.edu.in.
authors.forename: Yamini
authors.initials: Y
authors.lastname: Chand
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India. Electronic address: dipa@mcbl.iisc.ernet.in.
authors.forename: Dipshikha
authors.initials: D
authors.lastname: Chakravortty
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D044404:Genomic Islands / Q000502:physiology*; D046228:Microarray Analysis; D018832:Molecular Chaperones / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods*; D012475:Salmonella / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D018832:Molecular Chaperones; C094577:SicA protein, Salmonella typhimurium
keywords: Eigen vector centrality; Salmonella; Salmonella pathogenicity island; SicA; Type III secretion system