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Pushing the envelope: LPS modifications and their consequences

Abstract

The defining feature of the Gram-negative cell envelope is the presence of two cellular membranes, with the specialized glycolipid lipopolysaccharide (LPS) exclusively found on the surface of the outer membrane. The surface layer of LPS contributes to the stringent permeability properties of the outer membrane, which is particularly resistant to permeation of many toxic compounds, including antibiotics. As a common surface antigen, LPS is recognized by host immune cells, which mount defences to clear pathogenic bacteria. To alter properties of the outer membrane or evade the host immune response, Gram-negative bacteria chemically modify LPS in a wide variety of ways. Here, we review key features and physiological consequences of LPS biogenesis and modifications.

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Acknowledgements

The authors gratefully acknowledge funding from the National Institutes of Health (RO1s AI129940, AI138576, AI076322 to M.S.T.)

Reviewer information

Nature Reviews Microbiology thanks Mario Feldman, Marcin Grabowicz and Alessandra Polissi for their contribution to the peer review of this work.

Author information

Both authors researched data for the article, discussed the content, wrote the article and reviewed and edited the manuscript before submission.

Competing interests

The authors declare no conflicts of interest.

Correspondence to M. Stephen Trent.

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Glossary

Lipooligosaccharide

(LOS). A form of lipopolysaccharide with an extended core oligosaccharide, but lacking O antigen.

Outer membrane vesicles

(OMVs). Small, spherical outer membrane blebs that are released from Gram-negative bacterial cells and contain membrane and periplasmic components.

Small RNAs

(sRNAs). Typically short, non-coding RNA molecules that interact with mRNAs to regulate gene expression or interact with proteins to regulate activity.

Inflammasome

An intracellular, multiprotein complex in mammalian cells that recognizes microbial molecules and activates inflammatory responses, including pyroptosis and proinflammatory cytokines.

Toll-like receptor 4–myeloid differentiation factor 2

(TLR4–MD2). A pattern-recognition receptor of the innate immune system that recognizes lipopolysaccharide and lipooligosaccharide, initiating a robust signal cascade and inflammatory responses in mammals.

Pyroptosis

An inflammatory, programmed cell death that typically is associated with infection of intracellular pathogens.

Capsule

A thick layer of polysaccharides that surrounds a bacterial cell, also referred to as capsular polysaccharide.

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Fig. 1: Lipopolysaccharide biogenesis, structure and modifications.
Fig. 2: Regulation of lipopolysaccharide modifications.
Fig. 3: Consequences of lipopolysaccharide modifications.
Fig. 4: Summary of therapeutic strategies to target lipopolysaccharide biogenesis.