Leishmania parasites exchange drug-resistance genes through extracellular vesicles

Douanne, Noélie; Dong, George; Amin, Atia; Bernardo, Lorena; Blanchette, Mathieu; Langlais, David; Olivier, Martin; Fernández-Prada, Christopher

doi:10.1016/j.celrep.2022.111121

Cited by 45 publications

(42 citation statements)

References 62 publications

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“…EVs from C. auris drug-resistant strain induced amphotericin-B resistance to a susceptible strain 21 , but the mechanisms underlying this process remain largely unknown. Other examples of EVs associated with drug resistance come from the study of Leishmania parasites 24 , where EVs mediate the delivery of drug-resistance genes, leading to the emergence of resistant subpopulations 24 .…”

Section: Introductionmentioning

confidence: 99%

Coregulation of extracellular vesicle production and fluconazole susceptibility inCryptococcus neoformans

Rizzo

Trottier

Moyrand

et al. 2023

Preprint

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Resistance to fluconazole (FLC), the most widely used antifungal drug, is typically achieved by altering the azole drug target and/or drug efflux pumps. Recent reports have suggested a link between vesicular trafficking and antifungal resistance. Here, we identified novel Cryptococcus neoformans regulators of extracellular vesicle (EV) biogenesis that impact FLC resistance. In particular, the transcription factor Hap2 does not affect the expression of the drug target or efflux pumps, yet it impacts the cellular sterol profile. Subinhibitory FLC concentrations also downregulate EV production. Moreover, in vitro spontaneous FLC-resistant colonies showed altered EV production, and the acquisition of FLC resistance was associated with decreased EV production in clinical isolates. Finally, the reversion of FLC resistance was associated with increased EV production. These data suggest a model in which fungal cells can regulate EV production before regulating gene expression as a first line of defense against antifungal assault in this fungal pathogen.

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Section: Introductionmentioning

confidence: 99%

Coregulation of extracellular vesicle production and fluconazole susceptibility inCryptococcus neoformans

Rizzo

Trottier

Moyrand

et al. 2023

Preprint

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“…Protein release through exosomes has been described in trypanosomes when the secretome of the parasite was analyzed, revealing the release of leaderless proteins as well as exosome associated proteins such as Rab proteins, clathrin heavy chain, enolase, and heat-shock protein 70 [ 254 ]. Extracellular vesicular secretion has also been reported in T. cruzi [ 259 ], and in Leishmania it was recently demonstrated that genes encoding drug resistance can be passed between Leishmania cells via exosomes [ 263 ] – highlighting the potential importance of this phenomenon for multiple phenotypes. Molecules involved in this type of secretion include the components of the ESCRT complex (Endosomal Sorting Complex Required for Transport) [ 262 , 264 , 265 ].…”

Section: Secreted Factors and Evsmentioning

confidence: 99%

Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts

et al. 2023

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African trypanosomes are vector-borne protozoa, which cause significant human and animal disease across sub-Saharan Africa, and animal disease across Asia and South America. In humans, infection is caused by variants of Trypanosoma brucei , and is characterized by varying rate of progression to neurological disease, caused by parasites exiting the vasculature and entering the brain. Animal disease is caused by multiple species of trypanosome, primarily T. congolense , T. vivax, and T. brucei . These trypanosomes also infect multiple species of mammalian host, and this complexity of trypanosome and host diversity is reflected in the spectrum of severity of disease in animal trypanosomiasis, ranging from hyperacute infections associated with mortality to long-term chronic infections, and is also a main reason why designing interventions for animal trypanosomiasis is so challenging. In this review, we will provide an overview of the current understanding of trypanosome determinants of infection progression and severity, covering laboratory models of disease, as well as human and livestock disease. We will also highlight gaps in knowledge and capabilities, which represent opportunities to both further our fundamental understanding of how trypanosomes cause disease, as well as facilitating the development of the novel interventions that are so badly needed to reduce the burden of disease caused by these important pathogens.

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“…falciparum , T . brucei , and Giardia intestinalis , produce EVs laden with proteins [ 6 ], coding and noncoding RNAs [ 14 – 18 ], and/or DNA [ 19 – 21 ] during infections. They do so either autonomously, by using their own machinery [ 22 – 24 ], or possibly by exploiting their host’s system, just like viruses do [ 25 – 27 ].…”

Section: Ev Biogenesis In Parasitic Protozoamentioning

confidence: 99%

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

et al. 2023

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Extracellular vesicles (EVs) provide a central mechanism of cell–cell communication. While EVs are found in most organisms, their pathogenesis-promoting roles in parasites are of particular interest given the potential for medical insight and consequential therapeutic intervention. Yet, a key feature of EVs in human parasitic protozoa remains elusive: their mechanisms of biogenesis. Here, we survey the current knowledge on the biogenesis pathways of EVs secreted by the four main clades of human parasitic protozoa: apicomplexans, trypanosomatids, flagellates, and amoebae. In particular, we shine a light on findings pertaining to the Endosomal Sorting Complex Required for Transport (ESCRT) machinery, as in mammals it plays important roles in EV biogenesis. This review highlights the diversity in EV biogenesis in protozoa, as well as the related involvement of the ESCRT system in these unique organisms.

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Leishmania parasites exchange drug-resistance genes through extracellular vesicles

Cited by 45 publications

References 62 publications

Coregulation of extracellular vesicle production and fluconazole susceptibility inCryptococcus neoformans

Coregulation of extracellular vesicle production and fluconazole susceptibility inCryptococcus neoformans

Pathogenicity and virulence of African trypanosomes: From laboratory models to clinically relevant hosts

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

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