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  • Review Article
  • Published:

Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi

Nature Reviews Microbiology volume 13, pages 620–630 (2015)Cite this article

Subjects

Key Points

  • Extracellular vesicle (EV) research in Gram-positive bacteria, mycobacteria and fungi was neglected until recently, owing to the presumption that vesicles could not traverse the thick cell walls found in these organisms.

  • EVs are now understood to be produced by all types of microorganism, including those with thick cell walls, and are biologically active.

  • EVs from bacteria, mycobacteria and fungi contain virulence factors, such as toxins, that are involved in pathogenesis and elicit strong host immune responses. For example, Cryptococcus neoformans EVs carry the capsular polysaccharide glucuronoxylomannan, which is an important virulence factor.

  • Interaction of EVs with the host is specific to the microorganism from which the EVs were produced and is based on the lipid content and cargo of the EVs.

  • Research into EVs produced by microorganisms with thick cell walls is a very young field. By learning how these microorganisms use EVs, we hope that researchers will gain insight into pathogenesis, therapeutics and vaccines.

Abstract

Extracellular vesicles (EVs) are produced by all domains of life. In Gram-negative bacteria, EVs are produced by the pinching off of the outer membrane; however, how EVs escape the thick cell walls of Gram-positive bacteria, mycobacteria and fungi is still unknown. Nonetheless, EVs have been described in a variety of cell-walled organisms, including Staphylococcus aureus, Mycobacterium tuberculosis and Cryptococcus neoformans. These EVs contain varied cargo, including nucleic acids, toxins, lipoproteins and enzymes, and have important roles in microbial physiology and pathogenesis. In this Review, we describe the current status of vesiculogenesis research in thick-walled microorganisms and discuss the cargo and functions associated with EVs in these species.

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Figure 1: Cell wall structure of Gram-negative bacteria, Gram-positive bacteria, mycobacteria and fungi.
Figure 2: Extracellular vesicle formation and release: three non-mutually exclusive hypotheses.
Figure 3: Extracellular vesicle function.

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Acknowledgements

A.C. was supported by the US National Institutes of Health (awards 5R01HL059842, 5R01AI033774, 5R37AI033142 and 5R01AI052733). R.P.-R. was supported in part by the US National Institutes of Health (award 1R21AI115091).

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, 10461, New York, USA

    Lisa Brown & Rafael Prados-Rosales

  2. 67 West Street #304, Brooklyn, 11222, New York, USA

    Julie M. Wolf

  3. Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, 21205, Maryland, USA

    Arturo Casadevall

Authors
  1. Lisa Brown
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  2. Julie M. Wolf
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  3. Rafael Prados-Rosales
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  4. Arturo Casadevall
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Correspondence to Rafael Prados-Rosales or Arturo Casadevall.

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FURTHER INFORMATION

EVpedia

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Glossary

Virulence factors

Products that are important for infection by and survival of a pathogen. These factors can include adhesins, DNA, toxins and other molecules.

Biofilms

Surface-dwelling bacterial cultures that are highly resistant to disruption and removal. Biofilms can consist of a single species or a community of multiple microorganisms.

Cell wall

The rigid structure that surrounds a microorganism and has a role in cell shape and homeostasis.

Melanin

A pigmented molecule derived from laccase-assisted oxidation of dihydroxy phenol compounds. Melanin can protect cells against oxidative damage.

Multivesicular bodies

(MVBs). A subset of endosomes that contain membrane-bound intraluminal vesicles that originate by budding into the MVB. Typically, MVBs fuse with the cell membrane to release the intraluminal vesicles into the extracellular space.

B-band lipopolysaccharide

(B-band LPS). LPS that is highly charged at neutral pH owing to the presence of a large number of phosphate groups and long O side chains, in contrast to Aband LPS.

Siderophores

Iron-scavenging molecules produced by microorganisms. Some microorganisms can also steal siderophores from other microorganisms in order to obtain iron.

Basidiomycetes

Filamentous fungi that reproduce sexually via the formation of specialized cells called basidia, which bear external spores called basidiospores. Some basidiomycetes can also reproduce asexually.

Ascomycetes

Fungi that, when reproducing sexually, form a structure called an ascus in which the spores are formed. Some ascomycetes can also reproduce asexually.

Extracellular DNA

(eDNA). DNA that is present in the extracellular milieu and might function in intercellular communication. eDNA can also be a structural component of biofilms and neutrophil extracellular traps.

Penicillin-binding proteins

Proteins that are essential for bacterial cell wall biogenesis and also have the capacity to bind to penicillin.

Glucuronoxylomannan

(GXM). A polysaccharide that is produced by the pathogenic fungus Cryptococcus neoformans and is a major component of the cellular capsule.

Cytolysin

A toxin with the ability to lyse cells.

Mycolactone

A macrolide toxin that is produced by a group of mycobacteria and causes Buruli ulcers in humans. It is required for virulence, is cytotoxic and blocks the translocation of immune proteins into the endoplasmic reticulum as a mechanism of immunosuppression.

Cholesterol microdomains

Lipid domains in the cellular lipid bilayer that are enriched in cholesterol.

T helper 2 cell

(TH2 cells). A subset of CD4+ T cells that is of paramount importance for host defence against extracellular pathogens. TH2 cells secrete the cytokines interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10 and IL-13, leading to strong antibody responses.

TH1 cell

A subset of CD4+ effector T cells that is required for host defence against intracellular viral and bacterial pathogens. TH1 cells secrete cytokines such as interferon-γ (IFNγ), interleukin-2 (IL-2), IL-10 and lymphotoxin, promoting macrophage activation, nitric oxide production and cytotoxic T lymphocyte proliferation.

Granulomatous inflammation

The aggregation of mononuclear inflammatory cells, which can be accompanied by the infiltration of other leukocytes or by necrosis.

Koch phenomenon

A rapid inflammatory response that develops to a reinfection with Mycobacterium tuberculosis and that is marked by necrotic lesions. The response is caused by hypersensitivity to products of the tubercle bacillus.

Proteoliposomes

Synthetic liposomes with proteins embedded into the lipid bilayer.

Lipidic nanovesicles

Nanoscale lipid-bilayer spheres or liposomes.

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Brown, L., Wolf, J., Prados-Rosales, R. et al. Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi. Nat Rev Microbiol 13, 620–630 (2015). https://doi.org/10.1038/nrmicro3480

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