Manipulation of Host Cell Organelles by Intracellular Pathogens

In this article, we explore the unique adaptations of intracellular bacterial pathogens that manipulate conserved cellular pathways, organelles, and cargo to convert the phagosome into a pathogen-containing vacuole (PCV). The phagosome is a degradative organelle that rapidly acidifies as it delivers cargo to the lysosome to destroy microbes and cellular debris. However, to avoid this fate, intracellular bacterial pathogens hijack the key molecular modulators of intracellular traffic: small GTPases, phospholipids, SNAREs, and their associated effectors. Following uptake, pathogens that reside in the phagosome either remain associated with the endocytic pathway or rapidly diverge from the preprogrammed route to the lysosome. Both groups rely on effector-mediated mechanisms to meet the common challenges of intracellular life, such as nutrient acquisition, vacuole expansion, and evasion of the host immune response. Mycobacteria, Salmonella, and Coxiella serve as a lens through which we explore regulators of the canonical endocytic route and pathogens that seek to subvert it. On the other hand, pathogens such as Chlamydia, Legionella, and Brucella disconnect from the canonical endocytic route. This bifurcation is linked to extensive hijacking of the secretory pathway and repurposing of the PCV into specialized compartments that resemble organelles in the secretory network. Finally, each pathogen devises specific strategies to counteract host immune responses, such as autophagy, which aim to destroy these aberrant organelles. Collectively, each unique intracellular niche and the pathogens that construct them reflect the outcome of an aggressive and ongoing molecular arms race at the host-pathogen interface. Improving our understanding of these well-adapted pathogens can help us refine our knowledge of conserved cell biological processes.