DOI: 10.1073/pnas.0709530105. Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure

Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure

10.1073/pnas.0709530105

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The cell walls of mycobacteria form an exceptional permeability barrier, and they are essential for virulence. They contain extractable lipids and long-chain mycolic acids that are covalently linked to peptidoglycan via an arabinogalactan network. The lipids were thought to form an asymmetrical bilayer of considerable thickness, but this could never be proven directly by microscopy or other means. Cryo-electron tomography of unperturbed or detergent-treated cells of Mycobacterium smegmatis embedded in vitreous ice now reveals the native organization of the cell envelope and its delineation into several distinct layers. The 3D data and the investigation of ultrathin frozen-hydrated cryosections of M. smegmatis , Myobacterium bovis bacillus Calmette–Guérin, and Corynebacterium glutamicum identified the outermost layer as a morphologically symmetrical lipid bilayer. The structure of the mycobacterial outer membrane necessitates considerable revision of the current view of its architecture. Conceivable models are proposed and discussed. These results are crucial for the investigation and understanding of transport processes across the mycobacterial cell wall, and they are of particular medical relevance in the case of pathogenic mycobacteria.

Bibliography

Hoffmann, C., Leis, A., Niederweis, M., Plitzko, J. M., & Engelhardt, H. (2008). Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure. Proceedings of the National Academy of Sciences, 105(10), 3963â3967.

Authors 5

Christian Hoffmann (first)
Andrew Leis (additional)
Michael Niederweis (additional)
Jürgen M. Plitzko (additional)
Harald Engelhardt (additional)

References 44 Referenced 509

10.1016/S0163-7827(98)00008-3
10.1016/S0065-2911(08)60016-8
10.1046/j.1365-2958.2003.03662.x
10.1146/annurev.bi.64.070195.000333
D Minnikin The Biology of Mycobacteria, eds C Tatledge, J Stanford (Academic, London) Vol 1, 94–184 (1982). / The Biology of Mycobacteria by Minnikin D (1982)
10.1073/pnas.92.24.11254
10.1016/S0934-8840(11)80292-6
10.1111/j.1365-2958.1993.tb01647.x
10.1099/00221287-147-5-1365
10.1074/jbc.275.10.7224
10.1099/00221287-148-10-3089
10.1073/pnas.0305439101
10.1128/jb.174.20.6508-6517.1992
T Mineda, N Ohara, H Yukitake, T Yamada Microbiologica 21, 1–8 (1998). / Microbiologica by Mineda T (1998)
10.1128/iai.62.5.1542-1550.1994
10.1074/jbc.M206983200
10.1126/science.1094114
10.1074/jbc.M511642200
10.1016/j.febslet.2004.10.102
10.1038/sj.emboj.7600366
10.1128/JB.185.20.6112-6118.2003
10.1099/mic.0.2006/003541-0
10.1128/JB.00509-07
10.1128/JB.01600-06
10.1016/0966-842X(96)10031-7
RE Lee, PJ Brennan, GS Besra Curr Topics Microbiol Immunol 215, 1–27 (1996). / Curr Topics Microbiol Immunol by Lee RE (1996)
10.1016/S1367-5931(97)80055-5
10.1016/j.femsre.2003.10.001
10.1111/j.0022-2720.2004.01395.x
10.1128/jb.178.2.456-461.1996
10.1099/mic.0.27869-0
10.1021/j100133a034
10.1021/bm034514c
10.1016/S0168-1656(03)00163-9
10.1074/jbc.M100662200
10.1016/S1472-9792(02)00089-6
10.1016/S1438-4221(00)80122-8
10.1093/glycob/11.9.107R
10.1128/AEM.65.4.1530-1539.1999
10.1006/jsbi.1997.3933
AC Kak, M Slaney Principles of Computerized Tomographic Imaging (IEEE, New York, 1988). / Principles of Computerized Tomographic Imaging by Kak AC (1988)
10.1006/jsbi.2001.4406
10.1016/j.jsb.2007.08.013
10.1016/j.jsb.2004.10.006

Dates

Type	When
Created	17 years, 5 months ago (March 3, 2008, 8:54 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 5:02 p.m.)
Indexed	4 weeks, 1 day ago (July 24, 2025, 8 a.m.)
Issued	17 years, 5 months ago (March 11, 2008)
Published	17 years, 5 months ago (March 11, 2008)
Published Online	17 years, 5 months ago (March 11, 2008)
Published Print	17 years, 5 months ago (March 11, 2008)

Funders 0

None

BibTeX

@article{Hoffmann_2008, title={Disclosure of the mycobacterial outer membrane: Cryo-electron tomography and vitreous sections reveal the lipid bilayer structure}, volume={105}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0709530105}, DOI={10.1073/pnas.0709530105}, number={10}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Hoffmann, Christian and Leis, Andrew and Niederweis, Michael and Plitzko, Jürgen M. and Engelhardt, Harald}, year={2008}, month=mar, pages={3963–3967} }

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