4.5 Review

Vacuolar escape of foodborne bacterial pathogens

Journal

JOURNAL OF CELL SCIENCE
Volume 134, Issue 5, Pages -

Publisher

COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.247221

Keywords

Foodborne pathogen; Phagocytosis; Phagosomal escape; Vacuolar escape

Categories

Funding

  1. Netherlands Organization for Scientific Research (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) [016.Veni.192.026]
  2. Netherlands Organization for Health Research and Development (ZonMw) [04510011910005]
  3. Human Frontier Science Program (HFSP) [RGY0080/2018]
  4. Netherlands Organization for Scientific Research [NWO-ALW VIDI 864.14.001]
  5. European Research Council (ERC) under the European Union [862137]

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Intracellular pathogens such as Listeria monocytogenes, Salmonella enterica, Shigella spp., and Staphylococcus aureus use different strategies to survive and proliferate within host cells, with the strategy of vacuolar escape being particularly important for evading host-cell defenses and gaining access to nutrients. Understanding the molecular mechanisms of vacuolar membrane rupture by these pathogens could lead to the development of new therapeutic approaches to combat foodborne illnesses.
The intracellular pathogens Listeria monocytogenes, Salmonella enterica, Shigella spp. and Staphylococcus aureus are major causes of foodborne illnesses. Following the ingestion of contaminated food or beverages, pathogens can invade epithelial cells, immune cells and other cell types. Pathogens survive and proliferate intracellularly via two main strategies. First, the pathogens can remain in membrane-bound vacuoles and tailor organellar trafficking to evade host-cell defenses and gain access to nutrients. Second, pathogens can rupture the vacuolar membrane and proliferate within the nutrient-rich cytosol of the host cell. Although this virulence strategy of vacuolar escape is well known for L. monocytogenes and Shigella spp., it has recently become clear that S. aureus and Salmonella spp. also gain access to the cytosol, and that this is important for their survival and growth. In this Review, we discuss the molecular mechanisms of how these intracellular pathogens rupture the vacuolar membrane by secreting a combination of proteins that lyse the membranes or that remodel the lipids of the vacuolar membrane, such as phospholipases. In addition, we also propose that oxidation of the vacuolar membrane also contributes to cytosolic pathogen escape. Understanding these escape mechanisms could aid in the identification of new therapeutic approaches to combat foodborne pathogens.

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