Reviews pubs.acs.org/jpr
Mycobacterium tuberculosis-Specific Phagosome Proteome and Underlying Signaling Pathways Ying He,† Weimin Li,‡ Guojian Liao,§ and Jianping Xie*,† †
Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China ‡ Beijing Tuberculosis & Thoracic Tumor Research Institute, Tongzhou Qu, Beijing 101149 § Institute of Modern Biopharmaceuticals, School of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China S Supporting Information *
ABSTRACT: The phagosome is very important to host immunity and tissue homeostasis maintenance. The destiny of the phagosome is closely associated with the outcome of the pathogen within. Most pathogens are successfully delivered to the lysosome and destroyed via the fusion of the phagosome with the lysosome. Mycobacterium tuberculosis has evolved multiple tactics to deflect the normal fusion process, such as delaying the phagosome maturation and acidification, thereby evading the immune recognition and subsequent elimination. Identification of the specific constituents of M. tuberculosis phagosome and the underlying signaling pathways are pivotal to define the key molecular features of this process and better targets to control this recalcitrant pathogen. Proteomic profiling is a comprehensive approach to define the protein inventory. In this review, currently available mycobacteria-containing phagosome proteome data were compiled. Ten putative evolutionarily conserved phagosome proteins were summarized. Unique proteins of the M. tuberculosis-containing phagosome proteome were compiled via comparison with other phagosomes, especially the inert latex bead phagosome. Signaling events associated with these unique proteins, such as Rab GTPase and PI3P, were also found and discussed. The data will facilitate better characterization of the M. tuberculosis specific phagosome constituents and involved signaling, and hostderived targets for better tuberculosis control. KEYWORDS: Mycobacterium tuberculosis, phagosome proteome, signaling
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immune response.8−10 Though there are elegant proteomic studies on the phagosomes of other bacteria,11−14 significant challenges remain for M. tuberculosis phagosome proteome research: (a) What are the differences between the typical M. tuberculosis-containing phagosome and the phagosomes containing other intracellular pathogens such as Salmonella, Listeria or Legionnella? (b) What is the subtle variation between the M. tuberculosis specific phagosome and the attenuated vaccine strain BCG phagosome? (c) How are the M. tuberculosis specific phagosome components shaped and maintained, especially the phagosomal membrane? We aim to address these concerns in this review via the integration of available phagosome proteomic data.
INTRODUCTION Phagocytosis is an important host event to internalize and eliminate pathogens and foreign substances eventually. Phagosome is a specialized dynamic membrane-bound organelle dedicated to this end. The phagosome undergoes a complex maturation progress involving early endosomes (EE), late endosomes (LE), ultimately fusion with lysosomes (LS),1,2 and culminating in a degradable phagolysosome, where the engulfed materials can be degraded and ready for antigen presentation. Phagosome can effectively resolve most pathogens. However, a handful of intracellular pathogens such as the Mycobacterium tuberculosis can survive and thrive on this otherwise destructive niche. Tactics for survival, even replication within this hostile environment, vary with pathogens.3,4 M. tuberculosis excellently exemplifies such successful evasion,5 which can block the phagolysosome biogenesis and subvert the host bactericidal responses, including phagosome−lysosome fusion, apoptosis, and robust proinflammatory immune response.6,7 Proteomics represents a comprehensive methodology capable of itemizing the phagosome constituents and assessing the ability of the intracellular pathogen to modulate the host © 2012 American Chemical Society
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PUTATIVE EVOLUTIONARILY CONSERVED PHAGOSOME CORE PROTEOME Phagosome proteomes and their subcomponents have been intensively explored during the past decade. The number of identified proteins in mouse macrophage latex bead phagosome Received: December 13, 2011 Published: March 23, 2012 2635
dx.doi.org/10.1021/pr300125t | J. Proteome Res. 2012, 11, 2635−2643
about 150 85 206 159 179 73
Entamoeba histolytica HM1:IMSS and MyoIB+
Entamoeba histolytica HM1:IMSS
Human neutrophils isolated from fresh venous blood of healthy individuals
Entamoeba histolytica HM-1:IMSS, KU33, and HATAJI
Dictyostelium discoideum Ax2
Tetrahymena thermophila MN173 and Grl1 Ex4.1A
RAW264.7 mouse macrophage cells
Neutrophils isolated from buffy coats obtained from healthy blood donors S2 Drosophila embryonic hemocyte-derived cell line
J774A.1, murine macrophage cell line
RAW 264.7 murine macrophage
RAW 264.7 murine macrophage
Dendritic cells ex vivo generated from monocytes which were isolated from the blood or the buffy coats of a healthy donor
2005
2005
2006
2006
2006
2006
2007
2007
2008
2008
2009
2012
2007
unknown
Dictyostelium discoideum Ax2
2002
2636
328
2415
147
546
617
106
505
117
number of identifications
J774 mouse macrophage-like cell line
cell type
2001
publishing time instruments used
7-T linear ion trap ion cyclotron resonance Fourier transform mass spectrometer
LTQ-Or-bitrap mass spectrometer
LCQ ion trapmass spectrometer system with a nanospray ion source MALDI-TOF mass spectrometry, Q-TOF mass spectrometer equipped with a nano-ESI ion source Hybrid quadrupole−Q-TOF mass spectrometer with a NanoES ion source linear trapping quadrupole−Orbitrap mass spectrometer Linear IT followed by a Fourier transform-ion cyclotron resonance Q-TOF mass spectrometer equipped with a Nanosource modified with a nanospray adapter ESI Q-TOF mass spectrometer or an ESI linear ion trap mass spectrometer Q-TOF mass spectrometer
MALDI-TOF mass spectrometer, Q-TOF mass spectrometer Q-TOF mass spectrometer equipped with a nanoelectrospray ionization (ESI) ion source LCQ ion trap mass spectrometer system with a nanospray ion source LCQ ion trap mass spectrometer system with a nanospray ion source Voyager-DE STR MALDI-TOF instrument, Micromass CapLC and Q-TOF mass spectrometer
Table 1. Chronological Summary of the Characterized Latex Bead Phagosome Proteomes
Prefractionation, LC− MS/MS Prefractionation, LC− MS/MS 2DGE, MS and Prefractionation, LC− MS/MS Prefractionation, LC− MS/MS Prefractionation, LC− MS/MS
LC−MS/MS
Prefractionation, LC− MS/MS LC−MS/MS
2DGE, MS
2DGE, MS and Prefractionation, LC− MS/MS LC−MS/MS
LC−MS/MS
2DGE, LC−MS/MS
2DGE, MS
2DGE, MS
method used
Mascot
Mascot
Mascot
Mascot
Mascot
Mascot
Mascot
Mascot
Mascot
Sequest
Mascot
Sequest
Bioanalyst software Sequest
Pepfrag, Scan
tool used for identification
