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EcoSal Plus

Domain 2: Cell Architecture and Growth

Function and Biogenesis of Lipopolysaccharides

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  • Authors: Blake Bertani1, and Natividad Ruiz2
  • Editor: James M. Slauch3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Microbiology, The Ohio State University, Columbus, OH 43210; 2: Department of Microbiology, The Ohio State University, Columbus, OH 43210; 3: The School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL
  • Received 20 January 2018 Accepted 01 June 2018 Published 01 August 2018
  • Address correspondence to Natividad Ruiz, [email protected]
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  • Abstract:

    The cell envelope is the first line of defense between a bacterium and the world-at-large. Often, the initial steps that determine the outcome of chemical warfare, bacteriophage infections, and battles with other bacteria or the immune system greatly depend on the structure and composition of the bacterial cell surface. One of the most studied bacterial surface molecules is the glycolipid known as lipopolysaccharide (LPS), which is produced by most Gram-negative bacteria. Much of the initial attention LPS received in the early 1900s was owed to its ability to stimulate the immune system, for which the glycolipid was commonly known as endotoxin. It was later discovered that LPS also creates a permeability barrier at the cell surface and is a main contributor to the innate resistance that Gram-negative bacteria display against many antimicrobials. Not surprisingly, these important properties of LPS have driven a vast and still prolific body of literature for more than a hundred years. LPS research has also led to pioneering studies in bacterial envelope biogenesis and physiology, mostly using and as model systems. In this review, we will focus on the fundamental knowledge we have gained from studies of the complex structure of the LPS molecule and the biochemical pathways for its synthesis, as well as the transport of LPS across the bacterial envelope and its assembly at the cell surface.

  • Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018

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/content/journal/ecosalplus/10.1128/ecosalplus.ESP-0001-2018
2018-08-01
2018-10-21

Abstract:

The cell envelope is the first line of defense between a bacterium and the world-at-large. Often, the initial steps that determine the outcome of chemical warfare, bacteriophage infections, and battles with other bacteria or the immune system greatly depend on the structure and composition of the bacterial cell surface. One of the most studied bacterial surface molecules is the glycolipid known as lipopolysaccharide (LPS), which is produced by most Gram-negative bacteria. Much of the initial attention LPS received in the early 1900s was owed to its ability to stimulate the immune system, for which the glycolipid was commonly known as endotoxin. It was later discovered that LPS also creates a permeability barrier at the cell surface and is a main contributor to the innate resistance that Gram-negative bacteria display against many antimicrobials. Not surprisingly, these important properties of LPS have driven a vast and still prolific body of literature for more than a hundred years. LPS research has also led to pioneering studies in bacterial envelope biogenesis and physiology, mostly using and as model systems. In this review, we will focus on the fundamental knowledge we have gained from studies of the complex structure of the LPS molecule and the biochemical pathways for its synthesis, as well as the transport of LPS across the bacterial envelope and its assembly at the cell surface.

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Figures

Image of Figure 1
Figure 1

(A) Depiction of the Gram-negative cell envelope and its components. The inner membrane (IM) contains phospholipids, while the outer membrane (OM) contains phospholipids in the inner leaflet and lipopolysaccharide (LPS) in the outer leaflet. (B) Structure of prototypical LPS produced by (shown is the core structure associated with core type K-12).

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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Image of Figure 2
Figure 2

Modifications to the preceding structure made by each enzyme in the pathway are marked in red, with the exception of the last step, where the modifications made by LpxL and LpxM are colored in red and blue, respectively. Donor molecules are not shown. At low temperatures, LpxP acts instead of LpxL to add a C16:1 palmitoleoyl group instead of a lauroyl group.

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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Image of Figure 3
Figure 3

Numbers represent bond positions between sugars. Note that nonstoichiometric modifications are not shown. All linkages are α-anomeric unless preceded by the β symbol, which specifies the β-anomeric state. Enzyme names are boxed, with arrows indicating the linkages they catalyze. It is worth noting that, while the O-antigen ligation site is indicated, K-12 does not typically produce O antigen because of an ancestral mutation that inactivates its synthesis.

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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Figure 4

Shown are the known core types in (R1 to R4, K-12) and serovar Typhimurium and serovar Arizonae IIIA. Numbers represent bond positions between sugars. Note that nonstoichiometric modifications are not shown. All linkages are α-anomeric unless preceded by the β symbol, which specifies the β-anomeric state.

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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Image of Figure 5
Figure 5

GT stands for glycosyltransferase, and for the purposes of illustration represents all GTs required to generate the O antigen. [O] represents a repeating unit of the O antigen, while the subscript represents the number of repeats present (n being an arbitrary integer). Individual sugar units are represented by “S” inside a hexagon, and are shown bound to an arbitrary nucleotide carrier NDP. The lipid carrier is Und-P.

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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Figure 6

Shown are modifications made to lipid A described in the text, alongside the enzymes that mediate them in corresponding colors. (A) Modifications made to the glucosamine phosphates. While shown in their preferred positions, it is possible for either phosphate to be modified with either substituent. (B) Modifications made to the acyl groups. The X indicated for LpxO is a hydroxyl (-OH) when LpxO is active, and a hydrogen (-H) when it is not. When acyl chains are removed, the cleaved bond is shown as a dotted line. It is important to note that LpxP is part of the conserved Raetz pathway but only active at low temperatures, at which LpxP substitutes for LpxL to add a C16:1 palmitoleoyl group instead of a lauroyl group.

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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Figure 7

Shown is the conserved inner core oligosaccharide (and its linkage to lipid A) in black, with potential modifications being indicated in red (although the alternate rhamnose modification by WaaS when the second Kdo is modified with PEtN by EptB is shown in blue). Numbers represent bond positions between sugars. Enzymes mediating modifications are next to each linkage, and, when not associated with K-12, core type associations are listed in parentheses beside the modification.

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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Figure 8

Shown are representations of MsbA, which mediates the transport of core-lipid A across the IM, and the Lpt complex (LptBFGCADE), which mediates LPS extraction from the IM and its transport through the periplasm and OM. As described in the text, the O antigen can be synthesized on Und-P and transported across the IM by different pathways ( Fig. 5 ). If made, the O antigen is ligated to core-lipid A in the periplasmic leaflet of the IM by WaaL (not shown).

Citation: Bertani B, Ruiz N. 2018. Function and Biogenesis of Lipopolysaccharides, EcoSal Plus 2018; doi:10.1128/ecosalplus.ESP-0001-2018
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