Traveling into Outer Space: Unanswered Questions about Fungal Extracellular Vesicles

Rodrigues, Márcio L.; Godinho, Rodrigo Mezêncio; Zamith-Miranda, Daniel; Nimrichter, Leonardo

doi:10.1371/journal.ppat.1005240

Cited by 57 publications

(56 citation statements)

References 29 publications

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“…TEM analysis of MalaEx isolated using sucrose gradient fractions with density 1.11–1.20 g/ml used for exosomes38 revealed the presence of exosome-like vesicles as previously described29. The cellular origin of fungal EV and the mechanisms to transverse the thick cell wall remains unknown1039. Future studies are needed to reveal the control of production and release of these vesicles.…”

Section: Discussionmentioning

confidence: 73%

Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis

Rayner

Bruhn

Vallhov

et al. 2017

Sci Rep

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Malassezia is the dominant fungus in the human skin mycobiome and is associated with common skin disorders including atopic eczema (AE)/dermatitis. Recently, it was found that Malassezia sympodialis secretes nanosized exosome-like vesicles, designated MalaEx, that carry allergens and can induce inflammatory cytokine responses. Extracellular vesicles from different cell-types including fungi have been found to deliver functional RNAs to recipient cells. In this study we assessed the presence of small RNAs in MalaEx and addressed if the levels of these RNAs differ when M. sympodialis is cultured at normal human skin pH versus the elevated pH present on the skin of patients with AE. The total number and the protein concentration of the released MalaEx harvested after 48 h culture did not differ significantly between the two pH conditions nor did the size of the vesicles. From small RNA sequence data, we identified a set of reads with well-defined start and stop positions, in a length range of 16 to 22 nucleotides consistently present in the MalaEx. The levels of small RNAs were not significantly differentially expressed between the two different pH conditions indicating that they are not influenced by the elevated pH level observed on the AE skin.Extracellular vesicles (EV) are released not only from different mammalian cell-types but also from microorganisms and parasites and have the capacity to transfer complex biological information [1][2][3][4][5] . Various types of EV ranging in size from 20 nm to 1,000 nm in diameter have been described and are classified mainly on their mechanisms of biogenesis and their physiological functions 1,6 . Those designated exosomes are nanosized vesicles of 50-100 nm which are released extracellularly after fusion of multicellular endosomes with the cell membrane, whereas microvesicles (MV) are larger vesicles (100-1,000 nm) generated through outward budding of the plasma membrane 1,5 . Gram-negative bacteria produce MV by outward budding of the outer membrane and these vesicles are therefore referred to as outer membrane vesicles (OMV) with a diameter in the range of 20-500 nm 6 . Exosomes can be detected in body fluids such as urine, bronchoalveolar lavage fluid (BAL), breast milk and serum 7 . The functions of exosomes include immunoregulatory mechanisms such as modulation of antigen presentation, immune activation, immune suppression, immune surveillance and intercellular communication 6 . EV from microorganisms with thick cell walls, such as Gram-positive bacteria and fungi, have been associated with cytotoxicity, the invasion of host cells, and the transfer of virulence factors 2 . As seen with exosomes 1,8 , fungal EV have been observed to deliver functional messenger (m)RNAs and micro (mi)RNA-like RNAs to recipient cells 9,10 . miRNAs are small non-coding RNAs with a length between 20 and 22 nucleotides (nt) 11 . They are spliced from precursor sequences that form the stable hairpin necessary for transportation from the nucleus to the cytoplasm. After the miRNA has been c...

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Section: Discussionmentioning

confidence: 73%

Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis

Rayner

Bruhn

Vallhov

et al. 2017

Sci Rep

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“…We considered whether the shift from planktonic to pseudohyphal morphology, induced by the growth substrate, could be mediated by proteins or nucleic acids transported by EV. EV are involved in fungal pathogenesis as suggested by the identification of virulence factors in the EV cargo (Rodrigues, Godinho, Zamith‐Miranda, & Nimrichter, ). However, virulence is not the sole function in which EV are involved, since non‐pathogenic yeasts such as S. cerevisiae , also produce EV (Brown et al, ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of extracellular vesicles produced in the biofilm by the dimorphic yeast Pichia fermentans

Leone

Bellani

Muccifora

et al. 2017

Journal Cellular Physiology

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The yeast Pichia fermentans DISAABA 726 strain (P. fermentans) is a dimorphic yeast that under different environmental conditions may switch from a yeast-like to pseudohyphal morphology. We hypothesize that exosomes-like vesicles (EV) could mediate this rapid modification. EV are membrane-derived vesicles carrying lipids, proteins, mRNAs and microRNAs and have been recognized as important mediators of intercellular communication. Although it has been assumed for a long time that fungi release EV, knowledge of their functions is still limited. In this work we analyze P. fermentans EV production during growth in two different media containing urea (YCU) or methionine (YCM) where yeast-like or pseudohyphal morphology are produced. We developed a procedure to extract EV from the neighboring biofilm which is faster and more efficient as compared to the widely used ultracentrifugation method. Differences in morphology and RNA content of EV suggest that they might have an active role during dimorphic transition as response to the growth conditions. Our findings are coherent with a general state of hypoxic stress of the pseudohyphal cells.

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“…In fungi, EVs were first discovered a decade ago when searching for a solution to the problem of trans‐cell wall transport of macromolecules in the pathogen Cryptococcus neoformans (Rodrigues et al, ). Since then, EVs have been characterized in 11 additional fungal species, where they participate in unconventional mechanisms of molecular export of proteins, glycans, pigments, nucleic acids and lipids [reviewed in (Rodrigues et al, ; Zamith‐Miranda et al, )]. On the basis of the observation that several of these molecules correspond to virulence factors and/or to immunologically active components, EVs have been proposed as key regulators of physiopathological mechanisms during fungal infections (Oliveira, Freire‐de‐Lima, et al, ; Vargas et al, ; Matos Baltazar et al, ; Almeida et al, ).…”

Section: Fungal Extracellular Vesicles (Evs) As Biologically Active Cmentioning

confidence: 99%

A two‐way road: novel roles for fungal extracellular vesicles

Rodrigues

Casadevall

2018

Molecular Microbiology

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The biological functions of fungal extracellular vesicles (EVs) or exosomes have been mostly determined on the basis of the assumption that they are vehicles of trans-cell wall transport and molecular export. The possibility that fungal cells can bind to and internalize EVs remained largely unaddressed. Recent studies, however, demonstrated that fungal cells can internalize host-derived and/or fungal EVs through processes that profoundly modify their regular physiology. To illustrate this novel view, we discuss (i) the uptake of plant EVs by phytopathogenic fungi culminating in growth defects and virulence attenuation, (ii) the influence of EV internalization in prion transmission and biofilm formation in yeast cells, and (iii) the EV-mediated transfer of virulence in isolates of Cryptococcus gattii. These recent observations indicate that the functions exerted by EVs in fungal cells result from previously unknown mechanisms of bidirectional transport, opening new venues for the investigation of how EVs impact fungal physiology.

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Traveling into Outer Space: Unanswered Questions about Fungal Extracellular Vesicles

Cited by 57 publications

References 29 publications

Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis

Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis

Analysis of extracellular vesicles produced in the biofilm by the dimorphic yeast Pichia fermentans

A two‐way road: novel roles for fungal extracellular vesicles

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