Assembly and Maintenance of Lipids at the Bacterial Outer Membrane

Abstract

The outer membrane of Gram-negative bacteria is essential for their survival in harsh environments and provides intrinsic resistance to many antibiotics. This membrane is remarkable; it is a highly asymmetric lipid bilayer. The inner leaflet of the outer membrane contains phospholipids, whereas the fatty acyl chains attached to lipopolysaccharide (LPS) comprise the hydrophobic portion of the outer leaflet. This lipid asymmetry, and in particular the exclusion of phospholipids from the outer leaflet, is key to creating an almost impenetrable barrier to hydrophobic molecules that can otherwise pass through phospholipid bilayers. It has long been known that these lipids are not made in the outer membrane. It is now believed that conserved multisubunit protein machines extract these lipids after their synthesis is completed at the inner membrane and transport them to the outer membrane. A longstanding question is how the cell builds and maintains this asymmetric lipid bilayer in coordination with the assembly of the other components of the cell envelope. This Review describes the transenvelope lipid transport systems that have been identified to participate in outer-membrane biogenesis: LPS transport via the Lpt machine, and phospholipid transport via the Mla pathway and several recently proposed transporters.

Structural Modeling of the Treponema pallidum Outer Membrane Protein Repertoire: a Road Map for Deconvolution of Syphilis Pathogenesis and Development of a Syphilis Vaccine

“…Ab initio shape reconstruction from the SAXS data, using ten independent bead models Because T. pallidum lacks an LPS biosynthetic pathway (6), we were surprised to discover that TP0515, originally identified as a candidate OMP based on secondary structure predictions (43), is a structural ortholog for LptD (11). Moreover, as shown in Figure S4, with the exception of LptE, T. pallidum contains all of the components of the Lpt pathway (Table 1) (74). The 3D model of TP0515, built by an ab initio modeling program I-TASSER (Table 1) (46), contains the hallmark features of Gram-negative LptD described above (Fig.…”

Phospholipid transporter shifts into reverse

“…Subsequent biochemical studies of the inner membrane ABC transporter subunits revealed that the Mla system spontaneously moves phospholipids toward the outer membrane (anterograde flow), but the role of ATP binding and hydrolysis in this process was not apparent. The resulting debate as to whether the Mla system drives retrograde versus anterograde phospholipid transport has called for the reconstitution of the inner and outer membrane Mla components into proteoliposomes, as was achieved previously for the lipopolysaccharide (LPS) transport system 1 . In this issue of Nature Structural & Molecular Biology, Tang et al 2 report a high resolution cryo-EM structure of the Mla inner membrane ABC transporter complex.…”

“…xon degeneration is the process through which axon segments that are disconnected from the cell body, due to injury, stress or other events, are actively and rapidly degraded. First described by Waller in 1850 (hence also known as Wallerian degeneration) 1 , groundbreaking research over the past ten years has established that the protein SARM1 has a critical role in axon degeneration 2,3 and contributes to various neurological and neurodegenerative diseases (reviewed in refs. [4][5][6] ).…”

Conserved tandem arginines for PbgA/YejM allowSalmonellato regulate LpxC and control lipopolysaccharide biogenesis during infection

“…Divalent cations form salt-bridges between adjacent phosphates on lipid A molecules to provide lateral stability to the surface, and hydrophobic interactions between the acyl chains of LPS and GPL molecules establish the barrier (12,14,15). The biochemical properties of the OM enhance enterobacterial resistance to small hydrophobic antibiotics and promote virulence and disease pathogenesis (4,7,13,(16)(17)(18).…”

“…Und-P-linked O-antigen conjugates are flipped into the periplasmic leaflet of the IM and polymerized (13,24). S. Typhimurium uses at least two polymerases to produce three O-antigen LPS subtypes, the short (2-15 repeating units; RU), long (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), and very long (>100 RU) LPS modalities (4,24). The LPS structures are transported outward across the periplasm and inserted into the outer leaflet of the OM by the Lpt machinery (20)(21)(22).…”