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.

Inferring pathogen-host interactions between Leptospira interrogans and Homo sapiens using network theory

“…Since, experimentally verified Leptospira -human protein-protein interactions (PPIs) are not available easily, we used previously reported data for comparison with our predicted data to assess the accuracy and sensitivity. Our predicted data was found to have 25 proteins of L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni (strain Fiocruz L1-130) (LIC) which were previously reported for playing an important role in the survival of bacteria and also responsible for infection in human 43 .…”

“…For which we found 25 L. interrogans serogroup Icterohaemorrhagiae serovar Copenhageni (strain Fiocruz L1-130) (LIC) proteins having significant role in the survival and infection as reported in previous study of Mehrotra et al . 43 . As the coverage and accuracy of our predicted interactions were dependent on the previously reported experimental data on pathogen-host protein interactions.…”

Leptospiraspecies promote a pro‐inflammatory phenotype in human neutrophils

“…In addition, while little is known about the LPS composition in the saprophytic spp. of Leptospira, important differences with the pathogenic species have been described in the expression of their lipoproteins, which have been reported as virulence factors (Mehrotra, Ramakrishnan, Dhandapani, Srinivasan, & Madanan, 2017;Vk et al, 2018). In this context and considering the lack of studies about the including an increase in CD11b expression (Jamsa, Huotari, Savolainen, Syrjala, & Ala-Kokko, 2015;Weirich et al, 1998).…”

Prevalência De Leptospirose Canina Em Um Abrigo No Município De Uberlândia Mg

“…O gênero Leptospira foi dividido em duas espécies: cepas patogênicas que são as L. interrogans sensu lato e as cepas saprófitas que são as L. biflexas sensu lato (MEHROTRA et al, 2017). De acordo com Himani et al (2013) há 13 leptospiras patogênicas e mais de 260 sorovares, sendo os mais comuns que infectam cães o sorovar canicola e o sorovar icterohaemorragia, no entanto os cães podem ser infectados por outros sorovares.…”