A lipoprotein/β-barrel complex monitors lipopolysaccharide integrity transducing information across the outer membrane

2017

Annu. Rev. Microbiol.

Self Cite

241

229

The hallmark of Gram-negative bacteria and organelles such as mitochondria and chloroplasts is the presence of an outer membrane (OM). In bacteria such as Escherichia coli, the OM is a unique asymmetric lipid bilayer with lipopolysaccharide (LPS) in the outer leaflet. Integral, transmembrane proteins assume a β-barrel structure (OMPs) and their assembly is catalyzed by the heteropentomeric Bam complex containing the OMP BamA and four lipoproteins, BamB-E. How the Bam complex assembles a great diversity of OMPs into a membrane without an obvious energy source is a particularly challenging problem because folding intermediates are predicted to be unstable in either an aqueous or a hydrophobic environment. Two models have been put forward, the budding model based largely on structural data, and the BamA-assisted model based on genetic and biochemical studies. Here we offer a critical discussion of the pros and cons of each.

Section: Overall Architecture Of the Bam Complexmentioning

confidence: 99%

Outer Membrane Biogenesis

Konovalova

Kahne²,

2017

Annu. Rev. Microbiol.

Self Cite

241

229

“…The Rcs two-component phosphorelay uses the OM lipoprotein RcsF to detect defects throughout the envelope (28)(29)(30). Stress conditions are thought to enable RcsF to reach across the periplasm to promote activation of the RcsC IM histidine kinase, which then phosphorylates the RcsB response regulator, allowing it to control expression of Rcs regulon genes (28,30,31).…”

Section: Abundant Lolb Is Required To Prevent Mislocalization Of An Amentioning

confidence: 99%

Redefining the essential trafficking pathway for outer membrane lipoproteins

Grabowicz

Proc. Natl. Acad. Sci. U.S.A.

2017

103

142

The outer membrane (OM) of Gram-negative bacteria is a permeability barrier and an intrinsic antibiotic resistance factor. Lipoproteins are OM components that function in cell wall synthesis, diverse secretion systems, and antibiotic efflux pumps. Moreover, each of the essential OM machines that assemble the barrier requires one or more lipoproteins. This dependence is thought to explain the essentiality of the periplasmic chaperone LolA and its OM receptor LolB that traffic lipoproteins to the OM. However, we show that in strains lacking substrates that are toxic when mislocalized, both LolA and LolB can be completely bypassed by activating an envelope stress response without compromising trafficking of essential lipoproteins. We identify the Cpx stress response as a monitor of lipoprotein trafficking tasked with protecting the cell from mislocalized lipoproteins. Moreover, our findings reveal that an alternate trafficking pathway exists that can, under certain conditions, bypass the functions of LolA and LolB, implying that these proteins do not perform any truly essential mechanistic steps in lipoprotein trafficking. Instead, these proteins' key function is to prevent lethal accumulation of mislocalized lipoproteins.

“…While this review focuses on σ E and Cpx responses, it is notable that other signal transduction systems also respond to envelope damage and significantly remodel the envelope. Both the RcsBCDF phosphorelay and the PhoPQ TCS sense LPS layer damage inflicted by cationic antimicrobial peptides (CAMPs) and respond by inducing extracellular polysaccharide production and LPS modifying enzymes, respectively, to fortify the OM [9,10]. The EnvZ/OmpR TCS responds to osmotic challenge by regulating major OMP porins [11] .…”

Section: Monitoring the Cell Envelopementioning

confidence: 99%

“…Well characterized Rcs inducing cues include damage to the LPS cell surface layer caused by cationic antimicrobial peptides (cAMPs) and peptidoglycan cell wall biogenesis defects [97,98]. The OM lipoprotein RcsF is the sensor of these stresses at the cell surface and in the periplasm [9,84,86]. It is proposed that RcsF stress sensing allows the protein to interact with IgaA and thereby relieve inhibition of RcsC, initiating the signaling cascade.…”

Section: Figurementioning

confidence: 99%

Envelope Stress Responses: An Interconnected Safety Net

Grabowicz

Trends in Biochemical Sciences

2017

114

128

The Escherichia coli cell envelope is a protective barrier at the frontline of interaction with the environment. Fidelity of envelope biogenesis must be monitored to establish and maintain a contiguous barrier. Indeed, the envelope must also be repaired and modified in response to environmental assaults. Envelope stress responses (ESRs) sense envelope damage or defects and alter the transcriptome to mitigate stress. We will review recent insights into stress sensing mechanisms of the σE and Cpx systems and the interaction of these ESRs. Small RNAs (sRNAs) are increasingly prominent regulators of the transcriptional response to stress. These fast-acting regulators also provide avenues for inter-ESR regulation that could be important when cells face multiple contemporaneous stresses, as is the case during infection.