Abstract
Intracellular bacteria are responsible for many infectious diseases in humans and have developed diverse mechanisms to interfere with host defense pathways. In particular, intracellular vacuoles are an essential niche used by pathogens to alter cellular and organelle functions, which facilitate replication and survival. Mycobacterium tuberculosis (Mtb), the pathogen causing tuberculosis in humans, is not only able to modulate its intraphagosomal fate by blocking phagosome maturation but has also evolved strategies to successfully prevent clearance by immune cells and to establish long-term survival in the host. Mass spectrometry (MS)-based proteomics allows the identification and quantitative analysis of complex protein mixtures and is increasingly employed to investigate host–pathogen interactions. Major challenges are limited availability and purity of pathogen-containing compartments as well as the asymmetric ratio in protein abundance when comparing bacterial and host proteins during the infection. Recent advances in purification techniques and MS technology helped to overcome previous difficulties and enable the detailed proteomic characterization of infected host cells and their pathogen-containing vacuoles. Here, we summarize current findings of the proteomic analysis of Mycobacterium-infected host cells and highlight progress that has been made to study the protein composition of mycobacterial vacuoles. Current investigations focus on the pathogenicity during Mtb infection, which will allow to better understand pathogen-induced changes and immunomodulation of infected host cells. Consequently, future research in this field will have important implications on host response, pathogen survival, and persistence, induced adaptive immunity and metabolic changes of immune cells promoting the development of novel host-directed therapies in tuberculosis.
Highlights
Phagocytic cells, such as macrophages, dendritic cells, and neutrophils, represent the first line of defense against invading pathogens, such as Legionella pneumophila, Coxiella burnetti, and Leishmania donovani, by engulfing and eliminating them by phagocytosis
Research on mycobacterial infections includes an increasing number of Mass spectrometry (MS)-based approaches, which refine our understanding of the molecular mechanisms underlying Mycobacterium tuberculosis (Mtb) pathogenesis
Together with improvements on purity and reproducibility of sample preparations, in particular of mycobacteriacontaining vacuoles (MCVs) containing virulent Mtb strains, it is feasible to combine these methods with other techniques analyzing dynamics and impact of host–pathogen interactions
Summary
Phagocytic cells, such as macrophages, dendritic cells, and neutrophils, represent the first line of defense against invading pathogens, such as Legionella pneumophila, Coxiella burnetti, and Leishmania donovani, by engulfing and eliminating them by phagocytosis. Phagocytosis is a complex process divided in several steps, which is initiated by the innate recognition of microbial patterns, Proteomic Analysis of Mycobacterial Infection leading to the formation of microbe-containing vesicles These vesicles fuse successively with different endocytic compartments [early endosome (EE) and late endosome (LE), and lysosomes (LYSs)] to form a microbicidal organelle, the phagolysosome [1]. It is not surprising that numerous microbes developed a wide variety of strategies to adapt and manipulate the phagocytic process [3] Among these strategies induced by intracellular pathogens, the phagosome maturation arrest initiated by Mycobacterium tuberculosis (Mtb) infection allows the colonization of phagocytes and long-term survival within host cells [4]. Cellular extract J774.A1 treated by Mycobacterium tuberculosis (Mtb) lipid extract
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
