title: Comparison of Leptospira interrogans and Leptospira biflexa genomes: analysis of potential leptospiral-host interactions.
abstract: Leptospirosis, a potentially life-threatening disease, remains the most widespread zoonosis caused by pathogenic species of Leptospira. The pathogenic spirochaete, Leptospira interrogans, is characterized by its ability to permeate human host tissues rapidly and colonize multiple organs in the host. In spite of the efforts taken to comprehend the pathophysiology of the pathogen and the heterogeneity posed by L. interrogans, the current knowledge on the mechanism of pathogenesis is modest. In an attempt to contribute towards the same, we demonstrate the use of an established structure-based protocol coupled with information on subcellular localization of proteins and their tissue-specificity, in recognizing a set of 49 biologically feasible interactions potentially mediated by proteins of L. interrogans in humans. We have also presented means to adjudge the physicochemical viability of the predicted host-pathogen interactions, for selected cases, in terms of interaction energies and geometric shape complementarity of the interacting proteins. Comparative analyses of proteins of L. interrogans and the saprophytic spirochaete, Leptospira biflexa, and their predicted involvement in interactions with human hosts, aided in underpinning the functional relevance of leptospiral-host protein-protein interactions specific to L. interrogans as well as those specific to L. biflexa. Our study presents characteristics of the pathogenic L. interrogans that are predicted to facilitate its ability to persist in human hosts.
authors.affiliation: Indian Institute of Science Mathematics Initiative, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Prachi
authors.initials: P
authors.lastname: Mehrotra
authors.forename: Gayatri
authors.initials: G
authors.lastname: Ramakrishnan
authors.forename: Gunasekaran
authors.initials: G
authors.lastname: Dhandapani
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Srinivasan
authors.forename: Madathiparambil G
authors.initials: MG
authors.lastname: Madanan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D016680:Genome, Bacterial; D054884:Host-Pathogen Interactions; D006801:Humans; D007919:Leptospira / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007922:Leptospirosis / Q000378:metabolism* / Q000382:microbiology; D008958:Models, Molecular; D009928:Organ Specificity; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping
chemical_list: D001426:Bacterial Proteins