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The mycobacterial cell envelope — a moving target

Nature Reviews Microbiology volume 18, pages 47–59 (2020)Cite this article

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Abstract

Mycobacterium tuberculosis, the leading cause of death due to infection, has a dynamic and immunomodulatory cell envelope. The cell envelope structurally and functionally varies across the length of the cell and during the infection process. This variability allows the bacterium to manipulate the human immune system, tolerate antibiotic treatment and adapt to the variable host environment. Much of what we know about the mycobacterial cell envelope has been gleaned from model actinobacterial species, or model conditions such as growth in vitro, in macrophages and in the mouse. In this Review, we combine data from different experimental systems to build a model of the dynamics of the mycobacterial cell envelope across space and time. We describe the regulatory pathways that control metabolism of the cell wall and surface lipids in M. tuberculosis during growth and stasis, and speculate about how this regulation might affect antibiotic susceptibility and interactions with the immune system.

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Fig. 1: Model of the mycobacterial cell envelope.
Fig. 2: The cell envelope of Mycobacterium tuberculosis during active growth and growth stasis.
Fig. 3: Regulation of arabinogalactan and surface lipids in active growth and growth stasis.
Fig. 4: Regulation of peptidoglycan in active growth and growth stasis.
Fig. 5: Regulation of mycolic acids and trehalose mycolates in active growth and growth stasis.

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Acknowledgements

The authors thank P. Brennan for his guidance and suggestions, and S. Fortune and A. Carey for critical reading and feedback on the manuscript. C.C.B. is supported by grant 1R15GM131317_01 from the US National Institutes of Health. E.J.R. and C.L.D. are supported by grant U19 AI107774 from the US National Institutes of Health.

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Harvard University, Boston, MA, USA

    Charles L. Dulberger

  2. Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, USA

    Charles L. Dulberger & Eric J. Rubin

  3. Department of Microbiology, Harvard Medical School, Boston, MA, USA

    Eric J. Rubin

  4. Department of Biology, University of Texas at Arlington, Arlington, TX, USA

    Cara C. Boutte

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C.C.B. and C.L.D. wrote the manuscript and developed the figures. E.R.B. provided critical feedback and suggested changes.

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Glossary

Granuloma

A mass of tissue, typically formed in response to infection, inflammation or the presence of a foreign substance.

Aerosol transmission

Infection of susceptible individuals via pathogen-laden, airborne particles or droplets.

Mycobacterium smegmatis

A non-pathogenic, fast-growing mycobacterial species that is often used as a model for studying mycobacterial cell biology.

Subclinical infection

An infection in humans that contains live Mycobacterium tuberculosis cells but in which the patient exhibits no symptoms because the infection is contained by the immune system.

Transposon sequencing

A genetic approach for determining the essentiality of genes. It combines transposon insertion mutagenesis with deep sequencing.

MHC class II antigen presentation

A critical strategy used by the adaptive immune system to detect and respond to infection and other stresses. Antigen-presenting cells relay information to T cells via cell surface MHC class I and MHC class II protein complexes that present peptides from self and non-self proteins they have encountered.

Acid-fastness

The resistance of bacteria or other cell types to acid-based or ethanol-based decolorization methods used in laboratory staining procedures, such as the Gram stain. As the waxy mycolic acids render mycobacteria impervious to the Gram stain, Robert Koch and Paul Ehrlich developed acid-fast staining methods for identifying Mycobacterium tuberculosis in clinical samples.

Pathogen-associated molecular patterns

Highly conserved molecular signatures found in proteins, lipids and small molecules made by pathogens. The innate immune system has evolved protein-based machinery, such as the Toll-like receptor pathways, to detect and initiate immune responses to pathogen-associated molecular patterns.

Type I interferon

A large group of cytokines, signalling proteins, that allow immune cells to communicate and respond to bacterial and viral infections.

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Dulberger, C.L., Rubin, E.J. & Boutte, C.C. The mycobacterial cell envelope — a moving target. Nat Rev Microbiol 18, 47–59 (2020). https://doi.org/10.1038/s41579-019-0273-7

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