Prediction of Protein-Protein Interactions Between Human Host and Two Mycobacterial Organisms

Prediction of Protein-Protein Interactions Between Human Host and Two Mycobacterial Organisms

Oruganty Krishnadev (Indian Institute of Science, India), Shveta Bisht (Indian Institute of Science, India) and Narayanaswamy Srinivasan (Indian Institute of Science, India)
Copyright: © 2012 |Pages: 13
DOI: 10.4018/978-1-4666-1785-8.ch010
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Abstract

The genomes of many human pathogens have been sequenced but the protein-protein interactions across a pathogen and human are still poorly understood. The authors apply a simple homology-based method to predict protein-protein interactions between human host and two mycobacterial organisms viz., M.tuberculosis and M.leprae. They focused on secreted proteins of pathogens and cellular membrane proteins to restrict to uncovering biologically significant and feasible interactions. Predicted interactions include five mycobacterial proteins of yet unknown function, thus suggesting a role for these proteins in pathogenesis. The authors predict interaction partners for secreted mycobacterial antigens such as MPT70, serine proteases and other proteins interacting with human proteins, such as toll-like receptors, ras signalling proteins and immune maintenance proteins, that are implicated in pathogenesis. These results suggest that the list of predicted interactions is suitable for further analysis and forms a useful step in the understanding of pathogenesis of these mycobacterial organisms.
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Introduction

Tuberculosis (TB) has adversely affected human affairs since biblical times. WHO estimates that there were 1.7 million cases of death due to tuberculosis in 2007 and around 13 million cases of Tuberculosis globally, most of them from Africa and South East Asian regions (www.who.int/tb/publications/global_report/2009/key_points/en/index.html). The standard medication for TB followed worldwide is isoniazid and rifampicin. However, the emergence of multi drug resistant strains (LoBue, 2009) has prompted a worldwide attempt to develop newer and more effective drugs for the treatment of TB (Kamal, Azeera, Malik, Shaik, & Rao, 2008; Guy & Mallampalli, 2008). Further complications in tackling TB are due to the persistence of M.tuberculosis bacteria inside the macrophages, which makes drug delivery inefficient. Due to these reasons, there is an increased need to understand the molecular mechanism of persistence of M.tuberculosis inside the human macrophages and to evolve strategies to disrupt the host-pathogen interplay which leads to this persistence of the bacteria inside the host (Houben, Nguyen & Pieters, 2006; Pieters, 2008; Zahrt, 2008). Recent advances in understanding mycobacterium physiology (Young, Stark & Kirschner, 2008; Tailleux et al, 2008) including a computational study of protein-protein interactions in the pathogen (Cui, Zhang, Wang & He, 2008) may lead to a better understanding. However the molecular details of host-pathogen interactions for this organism are still not very well understood.

The host-pathogen interplay in the initial stages of infection in TB, is mainly due to glycolipids and/or lipoproteins (Józefowski, Sobota, & Kwiatkowska, 2008) with crucial roles believed to be mediated by secreted proteins. Thus, there is a need to understand the molecular details of protein-protein interactions occurring between the human host and bacterial pathogen.

Another diseases similar to TB is Leprosy, it affects mainly the neuronal cells and causes degeneration of the nerves. The organism causing leprosy is Mycobacterium leprae and is closely related to M.tuberculosis.

The detection of protein-protein interactions is not very efficient in such systems and novel procedures have been proposed for experimental detection of protein-protein interactions occurring among the proteins of M.tuberculosis (O'hare, Juillerat, Dianiskov_, & Johnsson, 2008). Such approaches and previously proposed methods (Suter, Kittanakom, & Stagljar, 2008; Lalonde et al., 2008) can be extended to detect protein -protein interactions occurring between the host and pathogen also, but to our knowledge has not been attempted so far on a genome scale. We cannot understand the pathophysiology of TB without a comprehensive list of protein-protein interactions (PPI) across the host and pathogen organisms, and in order to bridge the gap we applied a method we developed earlier (Krishnadev & Srinivasan, 2008) for the prediction of PPI across the host and pathogen organisms.

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