Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane?

Camacho, Abel Cruz; Alfandari, Daniel; Kozela, Ewa; Regev‐Rudzki, Neta

doi:10.1371/journal.ppat.1011140

Cited by 15 publications

(7 citation statements)

References 168 publications

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“…Another interesting discovery to the field is that a eukaryotic pathogen can manipulate the host ESCRT machinery. Protozoan parasites encode a reduced ESCRT machinery that is still functional in EV biogenesis [ 162 , 163 ]. Why does T .…”

Section: Discussionmentioning

confidence: 99%

The multifaceted interactions between pathogens and host ESCRT machinery

Rivera-Cuevas

Carruthers

2023

PLoS Pathog

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The Endosomal Sorting Complex Required for Transport (ESCRT) machinery consists of multiple protein complexes that coordinate vesicle budding away from the host cytosol. ESCRTs function in many fundamental cellular processes including the biogenesis of multivesicular bodies and exosomes, membrane repair and restoration, and cell abscission during cytokinesis. Work over the past 2 decades has shown that a diverse cohort of viruses critically rely upon host ESCRT machinery for virus replication and envelopment. More recent studies reported that intracellular bacteria and the intracellular parasite Toxoplasma gondii benefit from, antagonize, or exploit host ESCRT machinery to preserve their intracellular niche, gain resources, or egress from infected cells. Here, we review how intracellular pathogens interact with the ESCRT machinery of their hosts, highlighting the variety of strategies they use to bind ESCRT complexes using short linear amino acid motifs like those used by ESCRTs to sequentially assemble on target membranes. Future work exposing new mechanisms of this molecular mimicry will yield novel insight of how pathogens exploit host ESCRT machinery and how ESCRTs facilitate key cellular processes.

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Section: Discussionmentioning

confidence: 99%

The multifaceted interactions between pathogens and host ESCRT machinery

Rivera-Cuevas

Carruthers

2023

PLoS Pathog

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“…This preliminary implication of EVs in the expression of ART resistance in malaria parasites requires further validation. However, this finding has implicated EV biogenesis as a potential drug discovery space for mitigating the risk of ART resistance in malaria parasites [12,18,19].…”

Section: Is Extracellular Vesicle Biogenesis a New Druggable Space?mentioning

confidence: 99%

Extracellular Vesicles: Translational Agenda Questions for Three Protozoan Parasites

Tandoh,

Ibarra‐Meneses,

Langlais

et al. 2024

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The protozoan parasites Plasmodium falciparum, Leishmania spp. and Trypanosoma cruzi continue to exert a significant toll on the disease landscape of the human population in sub‐Saharan Africa and Latin America. Control measures have helped reduce the burden of their respective diseases—malaria, leishmaniasis and Chagas disease—in endemic regions. However, the need for new drugs, innovative vaccination strategies and molecular markers of disease severity and outcomes has emerged because of developing antimicrobial drug resistance, comparatively inadequate or absent vaccines, and a lack of trustworthy markers of morbid outcomes. Extracellular vesicles (EVs) have been widely reported to play a role in the biology and pathogenicity of P. falciparum, Leishmania spp. and T. cruzi ever since they were discovered. EVs are secreted by a yet to be fully understood mechanism in protozoans into the extracellular milieu and carry a cargo of diverse molecules that reflect the originator cell's metabolic state. Although our understanding of the biogenesis and function of EVs continues to deepen, the question of how EVs in P. falciparum, Leishmania spp. and T. cruzi can serve as targets for a translational agenda into clinical and public health interventions is yet to be fully explored. Here, as a consortium of protozoan researchers, we outline a plan for future researchers and pose three questions to direct an EV's translational agenda in P. falciparum, Leishmania spp. and T. cruzi. We opine that in the long term, executing this blueprint will help bridge the current unmet needs of these medically important protozoan diseases in sub‐Saharan Africa and Latin America.

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“…Nearly all living cells may excrete EVs, which are described based on their site of origin (i.e., exosomes, ectosomes, cytonemes & nanotubes) ( Vermeulen et al, 2020 .). However, only recently have EVs been recognized as participating in cell-to-cell communication processes, including between predator and prey ( de Souza and Barrias, 2020 ), and carry specific virulence factors ( Cruz Camacho et al., 2023 ) with known immunomodulatory properties ( Costa et al., 2021 ). Exosomes are EVs that originate from the endocytic pathway of a cell ( de Souza and Barrias, 2020 ; Cruz Camacho et al., 2023 ) and FLA-EVs are of focus here because of their likely multiple connections across the life cycle of L. pneumophila in biofilms of engineered environments ( Figure 1 ).…”

Section: Primary Role Of Free-living Amoebae Supporting Problematic ...mentioning

confidence: 99%

Conceptual model to inform Legionella–amoebae control, including the roles of extracellular vesicles in engineered water system infections

Ashbolt

2023

Front. Cell. Infect. Microbiol.

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Extracellular vesicles (EVs or exosomes) are well described for bacterial pathogens associated with our gastrointestinal system, and more recently as a novel mechanism for environmental persistence, dissemination and infection for human enteric viruses. However, the roles played by EVs in the ancient arms race that continues between amoebae and one of their prey, Legionella pneumophila, is poorly understood. At best we know of intracellular vesicles of amoebae containing a mix of bacterial prey species, which also provides an enhanced niche for bacteriophage infection/spread. Free-living amoeba-associated pathogens have recently been recognized to have enhanced resistance to disinfection and environmental stressors, adding to previously understood (but for relatively few species of) bacteria sequestered within amoebal cysts. However, the focus of the current work is to review the likely impacts of large numbers of respiratory-sized EVs containing numerous L. pneumophila cells studied in pure and biofilm systems with mixed prey species. These encapsulated pathogens are orders of magnitude more resistant to disinfection than free cells, and our engineered systems with residual disinfectants could promote evolution of resistance (including AMR), enhanced virulence and EV release. All these are key features for evolution within a dead-end human pathogen post lung infection. Traditional single-hit pathogen infection models used to estimate the probability of infection/disease and critical environmental concentrations via quantitative microbial risk assessments may also need to change. In short, recognizing that EV-packaged cells are highly virulent units for transmission of legionellae, which may also modulate/avoid human host immune responses. Key data gaps are raised and a previous conceptual model expanded upon to clarify where biofilm EVs could play a role promoting risk as well as inform a more wholistic management program to proactively control legionellosis.

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Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane?

Cited by 15 publications

References 168 publications

The multifaceted interactions between pathogens and host ESCRT machinery

The multifaceted interactions between pathogens and host ESCRT machinery

Extracellular Vesicles: Translational Agenda Questions for Three Protozoan Parasites

Conceptual model to inform Legionella–amoebae control, including the roles of extracellular vesicles in engineered water system infections

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