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Microorganisms
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Extracellular Vesicles in Pathogens
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Extracellular Vesicles in Pathogens

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Medical Microbiology".

Deadline for manuscript submissions: closed (15 February 2024) | Viewed by 12910

Special Issue Editor

Prof. Dr. Ana Claudia Torrecilhas

E-Mail Website
Guest Editor
Pharmacy School at Federal University of Sao Paulo (UNIFESP), Sao Paulo, Brazil
Interests: extracellular vesicles; infectious disease; immunology

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) define the structures, surrounded by a typical bilayer lipid membrane bearing integral proteins, which can carry diverse cargo outside the cell to distant sites. Although EVs have a diameter of 20–1000 nm. In microorganisms, EVs carry protein, glycoprotein, mRNA, and small RNA species, as mammalian EVs. The EV types are defined by their origin, i.e., exosomes, when derived from multivesicular bodies, microvesicles, and ectosomes, when derived from cell membrane budding or invagination, and apoptotic bodies. EVs can mediate intercellular communication through distant signaling both in physiological processes and pathological progression.

This Research Topics on Extracellular Vesicles in Pathogens encourages submissions of original articles or reviews covering all aspects related to these structures. The articles that focus on EVs from bacteria, fungi, parasites, and viruses. Subjects of special interest are the functional roles of EVs interaction with host cell, signaling and, characterization of EV subpopulations, variations in EV contents and morphology following specific culture conditions, EV markers, vaccination, biomarkers, diagnostic, clinical application, and Therapies.

Prof. Dr. Ana Claudia Torrecilhas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Microorganisms is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Extracellular Vesicles (EVs)
  • pathogens
  • immune response
  • biomarker
  • clinical application
  • host interaction and diagnostic

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Published Papers (7 papers)

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Research

Jump to: Review

18 pages, 7106 KiB  
Article
Exploring Peripheral Blood-Derived Extracellular Vesicles as Biomarkers: Implications for Chronic Chagas Disease with Viral Infection or Transplantation
by Rafael Pedro Madeira, Paula Meneghetti, Nicholy Lozano, Gislene M. Namiyama, Vera Lucia Pereira-Chioccola and Ana Claudia Torrecilhas
Microorganisms 2024, 12(1), 116; https://doi.org/10.3390/microorganisms12010116 - 5 Jan 2024
Cited by 1 | Viewed by 1561
Abstract
Extracellular vesicles (EVs) are lipid bilayer envelopes that encapsulate cell-specific cargo, rendering them promising biomarkers for diverse diseases. Chagas disease, caused by the parasite Trypanosoma cruzi, poses a significant global health burden, transcending its initial epicenter in Latin America to affect individuals [...] Read more.
Extracellular vesicles (EVs) are lipid bilayer envelopes that encapsulate cell-specific cargo, rendering them promising biomarkers for diverse diseases. Chagas disease, caused by the parasite Trypanosoma cruzi, poses a significant global health burden, transcending its initial epicenter in Latin America to affect individuals in Europe, Asia, and North America. In this study, we aimed to characterize circulating EVs derived from patients with chronic Chagas disease (CCD) experiencing a reactivation of acute symptoms. Blood samples collected in EDTA were processed to isolate plasma and subsequently subjected to ultracentrifugation for particle isolation and purification. The EVs were characterized using a nanoparticle tracking analysis and enzyme-linked immunosorbent assay (ELISA). Our findings revealed distinctive differences in the size, concentration, and composition of EVs between immunosuppressed patients and those with CCD. Importantly, these EVs play a critical role in the pathophysiology of Chagas disease and demonstrate significant potential as biomarkers in the chronic phase of the disease. Overall, our findings support the potential utility of the CL-ELISA assay as a specific sensitive tool for detecting circulating EVs in chronic Chagasic patients, particularly those with recurrent infection following an immunosuppressive treatment or with concurrent HIV and Chagas disease. Further investigations are warranted to identify and validate the specific antigens or biomarkers responsible for the observed reactivity in these patient groups, which may have implications for diagnosis, the monitoring of treatment, and prognosis. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Pathogens)
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18 pages, 3413 KiB  
Article
Extracellular Vesicles Released by Leishmania (Leishmania) amazonensis Promastigotes with Distinct Virulence Profile Differently Modulate the Macrophage Functions
by Rogéria Cristina Zauli, Isabelle Carlos de Souza Perez, Aline Correia Costa de Morais, Ana Carolina Ciaccio, Andrey Sladkevicius Vidal, Rodrigo Pedro Soares, Ana Claudia Torrecilhas, Wagner Luiz Batista and Patricia Xander
Microorganisms 2023, 11(12), 2973; https://doi.org/10.3390/microorganisms11122973 - 13 Dec 2023
Cited by 1 | Viewed by 1430
Abstract
Leishmania spp. is the aetiologic agent of leishmaniasis, a disease endemic in several developing countries. The parasite expresses and secretes several virulence factors that subvert the macrophage function and immune response. Extracellular vesicles (EVs) can carry molecules of the parasites that show immunomodulatory [...] Read more.
Leishmania spp. is the aetiologic agent of leishmaniasis, a disease endemic in several developing countries. The parasite expresses and secretes several virulence factors that subvert the macrophage function and immune response. Extracellular vesicles (EVs) can carry molecules of the parasites that show immunomodulatory effects on macrophage activation and disease progression. In the present work, we detected a significantly higher expression of lpg3 and gp63 genes in Leishmania amazonensis promastigotes recovered after successive experimental infections (IVD-P) compared to those cultured for a long period (LT-P). In addition, we observed a significantly higher percentage of infection and internalized parasites in groups of macrophages infected with IVD-P. Macrophages previously treated with EVs from LT-P showed higher percentages of infection and production of inflammatory cytokines after the parasite challenge compared to the untreated ones. However, macrophages infected with parasites and treated with EVs did not reduce the parasite load. In addition, no synergistic effects were observed in the infected macrophages treated with EVs and reference drugs. In conclusion, parasites cultured for a long period in vitro and recovered from animals’ infections, differently affected the macrophage response. Furthermore, EVs produced by these parasites affected the macrophage response in the early infection of these cells. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Pathogens)
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18 pages, 3470 KiB  
Article
Optimization of Enterotoxigenic Escherichia coli (ETEC) Outer Membrane Vesicles Production and Isolation Method for Vaccination Purposes
by Melibea Berzosa, Alberto Delgado-López, Juan Manuel Irache and Carlos Gamazo
Microorganisms 2023, 11(8), 2088; https://doi.org/10.3390/microorganisms11082088 - 15 Aug 2023
Cited by 1 | Viewed by 1947
Abstract
The study addresses Enterotoxigenic Escherichia coli (ETEC), a significant concern in low-income countries. Despite its prevalence, there is no licensed vaccine against ETEC. Bacterial vesicle-based vaccines are promising due to their safety and diverse virulence factors. However, cost-effective production requires enhancing vesicle yield [...] Read more.
The study addresses Enterotoxigenic Escherichia coli (ETEC), a significant concern in low-income countries. Despite its prevalence, there is no licensed vaccine against ETEC. Bacterial vesicle-based vaccines are promising due to their safety and diverse virulence factors. However, cost-effective production requires enhancing vesicle yield while considering altered properties due to isolation methods. The proposed method involves heat treatment and ultrafiltration to recover vesicles from bacterial cultures. Two vesicle types, collected from heat-treated (HT-OMV) or untreated (NT-OMV) cultures, were compared. Vesicles were isolated via ultrafiltration alone (“complete”) or with ultracentrifugation (“sediment”). Preliminary findings suggest complete HT-OMV vesicles are suitable for an ETEC vaccine. They express important proteins (OmpA, OmpX, OmpW) and virulence factors (adhesin TibA). Sized optimally (50–200 nm) for mucosal vaccination, they activate macrophages, inducing marker expression (CD40, MHCII, CD80, CD86) and Th1/Th2 cytokine release (IL-6, MCP-1, TNF-α, IL12p70, IL-10). This study confirms non-toxicity in RAW 264.7 cells and the in vivo ability of complete HT-OMV to generate significant IgG2a/IgG1 serum antibodies. Results suggest promise for a cost-effective ETEC vaccine, requiring further research on in vivo toxicity, pathogen-specific antibody detection, and protective efficacy. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Pathogens)
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15 pages, 1903 KiB  
Article
Comparative Analysis of Prokaryotic Extracellular Vesicle Proteins and Their Targeting Signals
by Ilias Stathatos and Vassiliki Lila Koumandou
Microorganisms 2023, 11(8), 1977; https://doi.org/10.3390/microorganisms11081977 - 31 Jul 2023
Cited by 4 | Viewed by 1511
Abstract
Prokaryotic extracellular vesicles (EVs) are vesicles that bud from the cell membrane and are secreted by bacteria and archaea. EV cargo in Gram-negative bacteria includes mostly periplasmic and outer membrane proteins. EVs are clinically important as their cargo can include toxins associated with [...] Read more.
Prokaryotic extracellular vesicles (EVs) are vesicles that bud from the cell membrane and are secreted by bacteria and archaea. EV cargo in Gram-negative bacteria includes mostly periplasmic and outer membrane proteins. EVs are clinically important as their cargo can include toxins associated with bacterial virulence and toxicity; additionally, they have been proposed as efficient vaccine agents and as the ancestors of the eukaryotic endomembrane system. However, the mechanistic details behind EV cargo selection and release are still poorly understood. In this study, we have performed bioinformatics analysis of published data on EV proteomes from 38 species of bacteria and 4 archaea. Focusing on clusters of orthologous genes (COGs) and using the EggNOG mapper function, we have identified cargo proteins that are commonly found in EVs across species. We discuss the putative role of these prominent proteins in EV biogenesis and function. We also analyzed the published EV proteomes for conserved signal sequences and discuss the potential role of these signal sequences for EV cargo selection. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Pathogens)
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13 pages, 1706 KiB  
Article
Mass Spectrometry Analysis Reveals Lipids Induced by Oxidative Stress in Candida albicans Extracellular Vesicles
by Gabriel Trentin, Tamires A. Bitencourt, Arthur Guedes, André M. Pessoni, Veronica S. Brauer, Alana Kelyene Pereira, Jonas Henrique Costa, Taicia Pacheco Fill and Fausto Almeida
Microorganisms 2023, 11(7), 1669; https://doi.org/10.3390/microorganisms11071669 - 27 Jun 2023
Cited by 3 | Viewed by 1754
Abstract
Candida albicans is a commensal fungus in healthy humans that causes infection in immunocompromised individuals through the secretion of several virulence factors. The successful establishment of infection is owing to elaborate strategies to cope with defensive molecules secreted by the host, including responses [...] Read more.
Candida albicans is a commensal fungus in healthy humans that causes infection in immunocompromised individuals through the secretion of several virulence factors. The successful establishment of infection is owing to elaborate strategies to cope with defensive molecules secreted by the host, including responses toward oxidative stress. Extracellular vesicle (EV) release is considered an alternative to the biomolecule secretory mechanism that favors fungal interactions with the host cells. During candidiasis establishment, the host environment becomes oxidative, and it impacts EV release and cargo. To simulate the host oxidative environment, we added menadione (an oxidative stress inducer) to the culture medium, and we explored C. albicans EV metabolites by metabolomics analysis. This study characterized lipidic molecules transported to an extracellular milieu by C. albicans after menadione exposure. Through Liquid Chromatography coupled with Mass Spectrometry (LC-MS) analyses, we identified biomolecules transported by EVs and supernatant. The identified molecules are related to several biological processes, such as glycerophospholipid and sphingolipid pathways, which may act at different levels by tuning compound production in accordance with cell requirements that favor a myriad of adaptive responses. Taken together, our results provide new insights into the role of EVs in fungal biology and host–pathogen interactions. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Pathogens)
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Review

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11 pages, 994 KiB  
Review
State of the Art on the Role of Staphylococcus aureus Extracellular Vesicles in the Pathogenesis of Atopic Dermatitis
by Marina Passos Torrealba, Fabio Seiti Yamada Yoshikawa, Valeria Aoki, Maria Notomi Sato and Raquel Leão Orfali
Microorganisms 2024, 12(3), 531; https://doi.org/10.3390/microorganisms12030531 - 6 Mar 2024
Cited by 1 | Viewed by 1569
Abstract
Atopic dermatitis (AD) is a chronic and relapsing inflammatory cutaneous disease. The role of host defense and microbial virulence factors in Staphylococcus aureus skin colonization, infection, and inflammation perpetuation in AD remains an area of current research focus. Extracellular vesicles (EV) mediate cell-to-cell [...] Read more.
Atopic dermatitis (AD) is a chronic and relapsing inflammatory cutaneous disease. The role of host defense and microbial virulence factors in Staphylococcus aureus skin colonization, infection, and inflammation perpetuation in AD remains an area of current research focus. Extracellular vesicles (EV) mediate cell-to-cell communication by transporting and delivering bioactive molecules, such as nucleic acids, proteins, and enzymes, to recipient cells. Staphylococcus aureus spontaneously secretes extracellular vesicles (SA-derived EVs), which spread throughout the skin layers. Previous research has shown that SA-derived EVs from AD patients can trigger cytokine secretion in keratinocytes, shape the recruitment of neutrophils and monocytes, and induce inflammatory AD-type lesions in mouse models, in addition to their role as exogenous worsening factors for the disease. In this review article, we aim to examine the role of SA-derived EVs in AD physiopathology and its progression, highlighting the recent research in the field and exploring the potential crosstalk between the host and the microbiota. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Pathogens)
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Graphical abstract

19 pages, 1587 KiB  
Review
Extracellular Vesicles: A Novel Mode of Viral Propagation Exploited by Enveloped and Non-Enveloped Viruses
by Shruti Chatterjee, Ramina Kordbacheh and Jon Sin
Microorganisms 2024, 12(2), 274; https://doi.org/10.3390/microorganisms12020274 - 28 Jan 2024
Cited by 5 | Viewed by 2472
Abstract
Extracellular vesicles (EVs) are small membrane-enclosed structures that have gained much attention from researchers across varying scientific fields in the past few decades. Cells secrete diverse types of EVs into the extracellular milieu which include exosomes, microvesicles, and apoptotic bodies. These EVs play [...] Read more.
Extracellular vesicles (EVs) are small membrane-enclosed structures that have gained much attention from researchers across varying scientific fields in the past few decades. Cells secrete diverse types of EVs into the extracellular milieu which include exosomes, microvesicles, and apoptotic bodies. These EVs play a crucial role in facilitating intracellular communication via the transport of proteins, lipids, DNA, rRNA, and miRNAs. It is well known that a number of viruses hijack several cellular pathways involved in EV biogenesis to aid in their replication, assembly, and egress. On the other hand, EVs can also trigger host antiviral immune responses by carrying immunomodulatory molecules and viral antigens on their surface. Owing to this intricate relationship between EVs and viruses, intriguing studies have identified various EV-mediated viral infections and interrogated how EVs can alter overall viral spread and longevity. This review provides a comprehensive overview on the EV-virus relationship, and details various modes of EV-mediated viral spread in the context of clinically relevant enveloped and non-enveloped viruses. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Pathogens)
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