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Review
. 2021 Mar 4:12:557902.
doi: 10.3389/fmicb.2021.557902. eCollection 2021.

Outer Membrane Vesicles of Gram-Negative Bacteria: An Outlook on Biogenesis

Eric Daniel Avila-Calderón  1   2 , María Del Socorro Ruiz-Palma  1   3 , Ma Guadalupe Aguilera-Arreola  1 , Norma Velázquez-Guadarrama  4 , Enrico A Ruiz  5 , Zulema Gomez-Lunar  1 , Sharon Witonsky  6   7 , Araceli Contreras-Rodríguez  1
Affiliations
Review

Outer Membrane Vesicles of Gram-Negative Bacteria: An Outlook on Biogenesis

Eric Daniel Avila-Calderón et al. Front Microbiol. .

Abstract

Outer membrane vesicles (OMVs) from Gram-negative bacteria were first described more than 50 years ago. However, the molecular mechanisms involved in biogenesis began to be studied only in the last few decades. Presently, the biogenesis and molecular mechanisms for their release are not completely known. This review covers the most recent information on cellular components involved in OMV biogenesis, such as lipoproteins and outer membrane proteins, lipopolysaccharide, phospholipids, quorum-sensing molecules, and flagella.

Keywords: LPS; OMVs biogenesis; PQS; bacterial vesicles; extracellular vesicles; flagellin; outer membrane vesicles; phospholipids.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Lipoproteins and outer membrane proteins are involved in OMV biogenesis. The Lpp, NlpI, OmpA, and Tol-Pal members maintain the stability of cellular envelopes joining the peptidoglycan layer with the inner membrane. Interruption or deletion of the genes encoding these proteins decrease the number of linkages, inducing OMV formation. For example, mutation of the pal gene decreases linkage with the outer membrane, leading to membrane protrusion and OMV release. Additionally, the accumulation of components in the periplasm, such as peptidoglycan precursors, triggers vesicle formation.
Figure 2
Figure 2
LPS modifications are implicated in OMV release. Negatively charged LPS causes an outer membrane imbalance, subsequent membrane protrusion, and OMV release. LPS modifications also contribute to OMV formation. (A) The S. typhimurium strain expressing PagL without the PhoPQ control produces more OMVs than the wild-type strain. The outer membrane of S. typhimurium expressing PagL shows that hexa-acylated lipid A is predominant, while OMVs primarily contain penta-acylated lipid A. Thus, either the cylindrical or inverted-cone shape decreases hydrophobic interactions, leading to membrane protrusion and favoring OMV formation. (B) Citrobacter rodentium uses a two-component system to modify LPS. PmrB, a member of this system, senses high Fe+3 concentrations and regulates the modification of lipid A. C. rodentium ΔpmrB cannot add groups to lipid A, leading to increased vesiculation.
Figure 3
Figure 3
Phospholipid transport regulates OMVs biogenesis. H. influenzae vacJ and yrbE mutants show a hypervesiculation phenotype because of the accumulation of phospholipids in the outer membrane. The vacJ and yrbE genes are involved in retrograde transport, maintaining membrane asymmetry. To trigger vesicle formation in the outer membrane, the transport of phospholipids from the inner membrane to the outer membrane should be significantly faster than phospholipid transport from the outer membrane to the inner membrane. Disorganization in phospholipid transport leads to the accumulation of phospholipids in the outer membrane, provoking OMV release.
See this image and copyright information in PMC

References

    1. Aschtgen M. S., Lynch J. B., Koc E., Schwartzman J., McFall-Ngai M., Ruby E. (2016). Rotation of Vibrio fischeri flagella produces outer membrane vesicles that induce host development. J. Bacteriol. 198, 2156–2165. 10.1128/JB.00101-16, PMID: - DOI - PMC - PubMed
    1. Avila-Calderón E. D., Araiza-Villanueva M. G., Cancino-Diaz J. C., López-Villegas E. O., Sriranganathan N., Boyle S. M., et al. . (2015). Roles of bacterial membrane vesicles. Arch. Microbiol. 197, 1–10. 10.1007/s00203-014-1042-7, PMID: - DOI - PubMed
    1. Banzhaf M., Yau H. C., Verheul J., Lodge A., Kritikos G., Mateus A., et al. . (2020). Outer membrane lipoprotein NlpI scaffolds peptidoglycan hydrolases within multi-enzyme complexes in Escherichia coli. EMBO J. 39:e102246. 10.15252/embj.2019102246, PMID: - DOI - PMC - PubMed
    1. Bernadac A., Gavioli M., Lazzaroni J. C., Raina S., Lloubès R. (1998). Escherichia coli tol-pal mutants form outer membrane vesicles. J. Bacteriol. 180, 4872–4878. 10.1128/JB.180.18.4872-4878.1998, PMID: - DOI - PMC - PubMed
    1. Bonnington K. E., Kuehn M. J. (2014). Protein selection and export via outer membrane vesicles. Biochim. Biophys. Acta. 1843, 1612–1619. 10.1016/j.bbamcr.2013.12.011 - DOI - PMC - PubMed

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