Lipopolysaccharide transport to the cell surface: biosynthesis and extraction from the inner membrane

Abstract

One contribution of 12 to a theme issue 'The bacterial cell envelope'. The cell surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS). The network of charges and sugars provided by the dense packing of LPS molecules in the outer leaflet of the outer membrane interferes with the entry of hydrophobic compounds into the cell, including many antibiotics. In addition, LPS can be recognized by the immune system and plays a crucial role in many interactions between bacteria and their animal hosts. LPS is synthesized in the inner membrane of Gram-negative bacteria, so it must be transported across their cell envelope to assemble at the cell surface. Over the past two decades, much of the research on LPS biogenesis has focused on the discovery and understanding of Lpt, a multi-protein complex that spans the cell envelope and functions to transport LPS from the inner membrane to the outer membrane. This paper focuses on the early steps of the transport of LPS by the Lpt machinery: the extraction of LPS from the inner membrane.

Outer Membrane Biogenesis

“…LPS is extracted from the IM by LptBFG. LPS is then translocated across the periplasm by being pushes by the following LPS molecule through the periplasmic LptA bridge to the OM translocon, LptD/LptE, which inserts LPS directly into the outer leaflet (see the recent reviews (62; 85). OM proteins, such as β-barrel OMPs (green) or lipoproteins (blue) are synthesized on ribosomes and contain a signal sequence (red) that targets them to the Sec complex, which translocates them across the IM.…”

Structural basis of MsbA-mediated lipopolysaccharide transport

“…In Gram-negative bacteria, LPS is the major component of the outer leaflet of the outer membrane, and plays a key role in constructing a proper envelope necessary for bacteria to survive in harsh environments 9,11 . The LPS biosynthesis and transport pathway is an attractive target for developing novel antibiotics 12,13 . In Escherichia coli , rough LPS (lipid A-inner core-outer core) is synthesized in the inner leaflet of the inner membrane, flipped by MsbA, further modified and then transported to the outer membrane (Extended Data Fig.…”

Synthesis and antimicrobial activity against Pseudomonas aeruginosa of macrocyclic β-hairpin peptidomimetic antibiotics containing N-methylated amino acids

“…4 The function of LptD has been studied most thoroughly in Escherichia coli, where in a complex with the lipoprotein LptE it fulfills the final step in the biogenesis of the OM, by translocating LPS molecules delivered by LptA from the periplasmic face into the outer leaflet of the asymmetric OM. 5,6 During exponential growth it has been estimated that in each cell typically ≈1200 LPS molecules per second are exported by LptD to the cell surface during OM biogenesis. 7 Recently the crystal structure of the full length LptD/E complex from Shigella flexneri was reported, which revealed a C-terminal 26-stranded ß-barrel integral membrane domain, conserved in other Gram-negative bacteria, with the lipoprotein LptE enclosed within the ß-barrel ( Figure 1C).…”