Improved understanding of pathogenesis from protein interactions inMycobacteriumtuberculosis

Abstract

Comprehensive mapping and analysis of protein-protein interactions provide not only systematic approaches for dissecting the infection and survival mechanisms of pathogens but also clues for discovering new antibacterial drug targets. Protein interaction data on Mycobacterium tuberculosis have rapidly accumulated over the past several years. This review summarizes the current progress of protein interaction studies on M. tuberculosis, the causative agent of tuberculosis. These efforts improve our knowledge on the stress response, signaling regulation, protein secretion and drug resistance of the bacteria. M. tuberculosis-host protein interaction studies, although still limited, have recently opened a new door for investigating the pathogenesis of the bacteria. Finally, this review discusses the importance of protein interaction data on identifying and screening new anti-tuberculosis targets and drugs, respectively.KEYWORDS: drug targets • Mycobacterium tuberculosis • pathogen-host interaction • protein-protein interaction • stress response Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is one of the most devastating human pathogens. In 2011, there were an estimated 8.7 million new cases of TB and 1.4 million people died from TB [1]. Sophisticated regulations allow M. tuberculosis to counter host-exerted harmful environments, interfere with host signaling pathways, evade immune clearance, survive and replicate in the host. Intracellular protein-protein interactions serve important functions in many complex cellular activities, such as stress response, cell signaling, transcriptional regulation, cell division, cell wall synthesis and protein secretion. In addition, interspecies pathogen-host protein interactions help the pathogen to interfere with host pathways and then evade host immune killing. Analyzing the human protein interactions involved in M. tuberculosis infection provides insights into the infection process. All these kinds of protein interaction data provide a basis for us to understand the molecular mechanisms of M. tuberculosis pathogenesis as well as clues for anti-TB drug design (FIGURE 1). In 1998, Cole et al. sequenced the complete genome of M. tuberculosis and found that this pathogen encodes approximately 4000 genes [2]. Since then, many studies have analyzed the interactions of these genes by using computational and highthroughput experimental technologies.Protein interaction data resource of M. tuberculosis Protein-protein interactions include physical interactions and functional interactions, in which physical interactions refer to the direct binding of two proteins and functional interactions mean these proteins are of functional relevance, for example, they are components of a same cell pathway. Unless specified otherwise, protein interactions in this review mean physical interactions. Obtaining protein-protein interaction data is important to elucidate the functions and mechanisms of this interaction in different cellular processes. The recent advances in the computa...

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