outer membrane
Research Article | Host-Microbe BiologyFusB Energizes Import across the Outer Membrane through Direct Interaction with Its Ferredoxin SubstrateThe ability to acquire iron is key to the ability of bacteria to cause infection. Plant-pathogenic Pectobacterium spp. are able to acquire iron from plants by transporting the iron-containing protein ferredoxin into the cell from proteolytic processing. In this work, we show that the TonB-like protein FusB plays a key role in transporting ferredoxin across the bacterial outer membrane by directly energizing its transport into...
Research Article | Therapeutics and PreventionOuter Membrane Disruption Overcomes Intrinsic, Acquired, and Spontaneous Antibiotic ResistanceThe spread of antibiotic resistance is an urgent threat to global health that necessitates new therapeutics. Treatments for Gram-negative pathogens are particularly challenging to identify due to the robust outer membrane permeability barrier in these organisms. Recent discovery efforts have attempted to overcome this hurdle by disrupting the outer membrane using chemical perturbants and have yielded several new peptides and small...
Minireview | Molecular Biology and PhysiologyEnterobacterial Common Antigen: Synthesis and Function of an Enigmatic MoleculeThe outer membrane (OM) of Gram-negative bacteria poses a barrier to antibiotic entry due to its high impermeability. Thus, there is an urgent need to study the function and biogenesis of the OM. In Enterobacterales, an order of bacteria with many pathogenic members, one of the components of the OM is enterobacterial common antigen (ECA). We have known of the presence of ECA on the cell surface of Enterobacterales for...
Research Article | Molecular Biology and PhysiologyAn Essential Membrane Protein Modulates the Proteolysis of LpxC to Control Lipopolysaccharide Synthesis in Escherichia coliThe outer membrane is a major determinant of the intrinsic antibiotic resistance of Gram-negative bacteria. It is composed of both lipopolysaccharide (LPS) and phospholipid, and the synthesis of these lipid species must be balanced for the membrane to maintain its barrier function in blocking drug entry. In this study, we identified an essential protein of unknown function as a key new factor in modulating LPS synthesis in the model...
Research Article | Molecular Biology and PhysiologyYejM Modulates Activity of the YciM/FtsH Protease Complex To Prevent Lethal Accumulation of LipopolysaccharideGram-negative bacteria are encapsulated by an outer membrane (OM) that is impermeable to large and hydrophobic molecules. As such, these bacteria are intrinsically resistant to several clinically relevant antibiotics. To better understand how the OM is established or maintained, we sought to clarify the function of the essential protein YejM in Escherichia coli. Here...
Research Article | Molecular Biology and PhysiologyGenetic and Chemical-Genetic Interactions Map Biogenesis and Permeability Determinants of the Outer Membrane of Escherichia coliGram-negative bacteria are a major concern for public health, particularly due to the rise of antibiotic resistance. It is important to understand the biology and permeability of the outer membrane of these bacteria in order to increase the efficacy of antibiotics that have difficulty penetrating this structure. Here, we studied the genetic interactions of a subset of outer membrane-related gene deletions in the model Gram-negative...
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...