Abstract
While most bacterial species taken up by macrophages are degraded through processing of the bacteria-containing vacuole through the endosomal-lysosomal degradation pathway, intravacuolar pathogens have evolved to evade degradation through the endosomal-lysosomal pathway. All intra-vacuolar pathogens possess specialized secretion systems (T3SS-T7SS) that inject effector proteins into the host cell cytosol to modulate myriad of host cell processes and remodel their vacuoles into proliferative niches. Although intravacuolar pathogens utilize similar secretion systems to interfere with their vacuole biogenesis, each pathogen has evolved a unique toolbox of protein effectors injected into the host cell to interact with, and modulate, distinct host cell targets. Thus, intravacuolar pathogens have evolved clear idiosyncrasies in their interference with their vacuole biogenesis to generate a unique intravacuolar niche suitable for their own proliferation. While there has been a quantum leap in our knowledge of modulation of phagosome biogenesis by intravacuolar pathogens, the detailed biochemical and cellular processes affected remain to be deciphered. Here we discuss how the intravacuolar bacterial pathogens Salmonella, Chlamydia, Mycobacteria, Legionella, Brucella, Coxiella, and Anaplasma utilize their unique set of effectors injected into the host cell to interfere with endocytic, exocytic, and ER-to-Golgi vesicle traffic. However, Coxiella is the main exception for a bacterial pathogen that proliferates within the hydrolytic lysosomal compartment, but its T4SS is essential for adaptation and proliferation within the lysosomal-like vacuole.
Highlights
Immune cells are equipped with a variety of receptors that recognize foreign material and particles permitting them to internalize the particles into a plasma-membrane derived vacuole that follows a maturation process that yields a phagolysosome (Vieira et al, 2002)
Bacterial effector proteins modulate a myriad of host cell processes and play an essential role in mediating vesicle trafficking pathways controlled by Rab GTPases and V-ATPases involved in phagosome biogenesis (Weber et al, 2009; Rama et al, 2015)
The first injected group of effectors is delivered across the epithelial plasma membrane by the T3SS1 (Lou et al, 2019) to modulate host signal transduction pathways, including the activation of Rho family GTPases, to induce actin rearrangements that drive the ruffling of the cell surface, IAM formation, and the uptake of the bacteria into a Salmonella-containing vacuole (SCV) (Schlumberger and Hardt, 2006; Ramos-Morales, 2012; Stevenin et al, 2019)
Summary
Immune cells are equipped with a variety of receptors that recognize foreign material and particles permitting them to internalize the particles into a plasma-membrane derived vacuole that follows a maturation process that yields a phagolysosome (Vieira et al, 2002). Bacterial effector proteins modulate a myriad of host cell processes and play an essential role in mediating vesicle trafficking pathways controlled by Rab GTPases and V-ATPases involved in phagosome biogenesis (Weber et al, 2009; Rama et al, 2015).
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