Phagosome proteomics: A powerful tool to assess bacteria-mediated immunomodulation

Abstract

Bacteria-mediated immunomodulation has important implications in microbial infection and bacterial vaccines. Intraphagosomal bacteria negotiate survival niches with the intracellular environment by modulating the phagosome composition during invasion. The final phagosome composition determines the fate of the intraphagosomal bacterium or the efficacy of a bacterial vaccine. Therefore, the phagosome proteome is a valuable readout to assess the ability of a natural or genetically engineered bacterial strain to modulate the host immune response. Compared to a preparation of latex-bead-containing phagosomes, the preparation of bacterial phagosomes requires additional measures to ensure comparable purity due to their closer density to some other organelles. This bottleneck can be overcome with delicate preparation protocols, proper experimental designs to facilitate bioinformatics based discrimination against contaminating proteins, and the incorporation of stable-isotope labeled internal standards to correct for contaminating fractions of phagosomal proteins. The rapid progress in the proteomics and bioinformatics fields provides an array of techniques that promise to bring about an unprecedented coverage of both known and as yet undiscovered immunomodulation pathways within bacterial phagosome proteomes. A precise portrait of the bacteria-mediated immunomodulation pathways in phagosomes will likely aid in the intelligent design of bioengineered bacterial vaccine strains for important future biomedical applications.

Mass spectrometry-based proteomic approaches to study pathogenic bacteria-host interactions

“…Additionally, they also identified many Legionella effectors and proteins that are associated with phosphorus metabolism. In principle, the approach described above can be readily applied to study other bacteria-containing phagosome and such studies are likely to shed new light on the complex biogenesis of bacterial vacuoles (Li, 2011 ).…”

Mycobacterium tuberculosis-Specific Phagosome Proteome and Underlying Signaling Pathways

“…Proteomics represents a comprehensive methodology capable of itemizing the phagosome constituents and assessing the ability of the intracellular pathogen to modulate the host immune response. − Though there are elegant proteomic studies on the phagosomes of other bacteria, − 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?…”