outer membrane
Research Article | Therapeutics and PreventionNovel Cassette Assay To Quantify the Outer Membrane Permeability of Five β-Lactams Simultaneously in Carbapenem-Resistant Klebsiella pneumoniae and Enterobacter cloacaeAntimicrobial resistance is causing a global human health crisis and is affecting all antibiotic classes. While β-lactams have been commonly used against susceptible isolates of Klebsiella pneumoniae and Enterobacter cloacae, carbapenem-resistant isolates are spreading worldwide and pose substantial...
Research Article | Molecular Biology and PhysiologySequential Translocation of Polypeptides across the Bacterial Outer Membrane through the Trimeric Autotransporter PathwayTrimeric autotransporter adhesins (TAAs) are specialized bacterial outer membrane proteins consisting of three identical subunits. TAAs contain large extracellular domains that trimerize and promote virulence, but the mechanism by which they are secreted is poorly understood. We found that the extracellular domains of a native TAA were secreted rapidly but that disordered and artificially folded polypeptides fused to native passenger...
Research Article | Molecular Biology and PhysiologyCombining Mutations That Inhibit Two Distinct Steps of the ATP Hydrolysis Cycle Restores Wild-Type Function in the Lipopolysaccharide Transporter and Shows that ATP Binding Triggers TransportGram-negative bacteria are naturally resistant to many antibiotics because their surface is covered by the glycolipid LPS. Newly synthesized LPS is transported across the cell envelope by the multiprotein Lpt machinery, which includes LptB2FGC, an unusual ABC transporter that extracts LPS from the inner membrane. Like in other ABC transporters, the LptB2FGC transport cycle is driven by the cyclical conformational...
Commentary | Molecular Biology and PhysiologyEmerging Roles for NlpE as a Sensor for Lipoprotein Maturation and Transport to the Outer Membrane in Escherichia coliOuter membrane biogenesis is a complex process for Gram-negative bacteria as the components are synthesized in the cytoplasm or at the inner membrane and then transported to the outer membrane. Stress pathways monitor and respond to problems encountered in assembling the outer membrane. The two-component system CpxAR was recently reported to be a stress pathway for transport of lipoproteins to the outer membrane, but it was unclear how...
Research Article | Molecular Biology and PhysiologyA Stress Response Monitoring Lipoprotein Trafficking to the Outer MembraneThe outer membrane built by Gram-negative bacteria such as Escherichia coli forms a barrier that prevents antibiotics from entering the cell, limiting clinical options at a time of prevalent antibiotic resistance. Stress responses ensure that barrier integrity is continuously maintained. We have identified the Cpx signal transduction system as a stress response that...
Research Article | Molecular Biology and PhysiologyCorrect Sorting of Lipoproteins into the Inner and Outer Membranes of Pseudomonas aeruginosa by the Escherichia coli LolCDE Transport SystemGram-negative bacteria build their outer membranes (OM) from components that are initially located in the inner membrane (IM). A fraction of lipoproteins is transferred to the OM by the transport machinery consisting of LolABCDE proteins. Our work demonstrates that the LolCDE complexes of the transport pathways of Escherichia coli and...
Commentary | Molecular Biology and PhysiologyAn “Uncommon” Role for Cyclic Enterobacterial Common Antigen in Maintaining Outer Membrane IntegrityAlthough discovered over 50 years ago, the physiological role of enterobacterial common antigen, a surface antigen produced by all members of the Enterobacteriaceae, has been poorly understood. In the work of Mitchell et al. (mBio 9:e01321-18, 2018, https://doi.org/10.1128/mBio.01321-18), the cyclized version of enterobacterial common antigen has been shown to play a role in...
- Research ArticleThe Escherichia coli Phospholipase PldA Regulates Outer Membrane Homeostasis via Lipid Signaling
The outer membrane of Gram-negative bacteria is an effective permeability barrier that protects the cell from toxic agents, including antibiotics. Barrier defects are often manifested by phospholipids present in the outer leaflet of this membrane that take up space normally occupied by lipopolysaccharide. We have discovered a signaling mechanism that operates across the entire cell envelope used by the cell to detect these outer...