Mycobacterium tuberculosis-Specific Phagosome Proteome and

Publication Date (Web): March 23, 2012 ... The phagosome is very important to host immunity and tissue homeostasis maintenance. ... The data will faci...
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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



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



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