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Published on: October 21, 2022
Interaction of microbial pathogens with host exocytic pathways
Keith Ireton1, Hoan Van Ngo1, Manmeet Bhalla1
1Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Abstract:
Many microbial pathogens co-opt or perturb host membrane trafficking pathways. This review covers recent examples in which microbes interact with host exocytosis, the fusion of intracellular vesicles with the plasma membrane. The bacterial pathogens Listeria monocytogenes and Staphylococcus aureus subvert recycling endosomal pathways of exocytosis in order to induce their entry into human cells. By contrast, entry of the protozoan pathogen Trypanosoma cruzi or the virus adenovirus into host cells involves exploitation of lysosomal exocytosis. Toxins produced by Bacillus anthracis or Vibrio cholerae interfere with exocytosis pathways mediated by the GTPase Rab11 and the exocyst complex. By doing so, anthrax or cholera toxins impair recycling of cadherins to cell-cell junctions and disrupt the barrier properties of endothelial cells or intestinal epithelial cells, respectively. Uropathogenic Escherichia coli (UPEC) is expelled from bladder epithelial cells through two different exocytic routes that involve sensing of bacteria in vacuoles by host Toll-like receptor 4 (TLR4) or monitoring of the pH of lysosomes harbouring UPEC. The TLR4 pathway is mediated by multiple Rab GTPases and the exocyst, whereas the other pathway involves exocytosis of lysosomes. Expulsion of UPEC through these pathways is thought to benefit the host.
Insights
Microbes manipulate host exocytosis, a key membrane trafficking process, for entry or to disrupt cell functions. Understanding these interactions reveals host defense mechanisms against pathogens like Listeria and E. coli.
Area of Science:
- Microbiology
- Cell Biology
- Pathogenesis
Background:
- Microbial pathogens frequently exploit host cell machinery.
- Membrane trafficking, particularly exocytosis, is crucial for cellular functions and host-pathogen interactions.
Purpose of the Study:
- To review recent examples of microbial interactions with host exocytosis.
- To highlight how pathogens subvert or utilize exocytic pathways for invasion, toxin delivery, or host defense.
Main Methods:
- Literature review of microbial interactions with host exocytosis.
- Analysis of specific examples involving bacterial, protozoan, and viral pathogens.
- Focus on molecular mechanisms involving Rab GTPases and the exocyst complex.
Main Results:
- Listeria monocytogenes and Staphylococcus aureus use recycling endosomal exocytosis for host cell entry.
- Trypanosoma cruzi and adenovirus exploit lysosomal exocytosis for entry.
- Bacillus anthracis and Vibrio cholerae toxins disrupt exocytosis, impairing cell barrier functions.
- Uropathogenic Escherichia coli (UPEC) is expelled via TLR4-mediated or lysosomal exocytosis pathways.
Conclusions:
- Microbial pathogens exhibit diverse strategies to manipulate host exocytosis.
- Host exocytic pathways are critical targets for pathogen invasion and manipulation.
- Understanding these interactions can inform the development of host-directed therapies.
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