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outer membrane

  • Open Access
    Predictive Rules of Efflux Inhibition and Avoidance in <span class="named-content genus-species" id="named-content-1">Pseudomonas aeruginosa</span>
    Research Article | Therapeutics and Prevention
    Predictive Rules of Efflux Inhibition and Avoidance in Pseudomonas aeruginosa

    Efflux pump avoidance and inhibition are desired properties for the optimization of antibacterial activities against Gram-negative bacteria. However, molecular and physicochemical interactions defining the interface between compounds and efflux pumps remain poorly understood. We identified properties that correlate with efflux avoidance and inhibition, are predictive of similar features in structurally diverse compounds, and allow...

    Jitender Mehla, Giuliano Malloci, Rachael Mansbach, Cesar A. López, Ruslan Tsivkovski, Keith Haynes, Inga V. Leus, Sally B. Grindstaff, Robert H. Cascella, Napoleon D’Cunha, Liam Herndon, Nicolas W. Hengartner, Enrico Margiotta, Alessio Atzori, Attilio V. Vargiu, Pedro D. Manrique, John K. Walker, Olga Lomovskaya, Paolo Ruggerone, S. Gnanakaran, Valentin V. Rybenkov, Helen I. Zgurskaya
  • Open Access
    Restoring Balance to the Outer Membrane: YejM’s Role in LPS Regulation
    Perspective | Molecular Biology and Physiology
    Restoring Balance to the Outer Membrane: YejM’s Role in LPS Regulation

    Gram-negative bacteria produce an asymmetric outer membrane (OM) that is particularly impermeant to many antibiotics and characterized by lipopolysaccharide (LPS) exclusively at the cell surface. LPS biogenesis remains an ideal target for therapeutic intervention, as disruption could kill bacteria or increase sensitivity to existing antibiotics.

    Brent W. Simpson, Martin V. Douglass, M. Stephen Trent
  • Open Access
    FusB Energizes Import across the Outer Membrane through Direct Interaction with Its Ferredoxin Substrate
    Research Article | Host-Microbe Biology
    FusB Energizes Import across the Outer Membrane through Direct Interaction with Its Ferredoxin Substrate

    The 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...

    Marta Wojnowska, Daniel Walker
  • Open Access
    Outer Membrane Disruption Overcomes Intrinsic, Acquired, and Spontaneous Antibiotic Resistance
    Research Article | Therapeutics and Prevention
    Outer Membrane Disruption Overcomes Intrinsic, Acquired, and Spontaneous Antibiotic Resistance

    The 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...

    Craig R. MacNair, Eric D. Brown
  • Open Access
    Enterobacterial Common Antigen: Synthesis and Function of an Enigmatic Molecule
    Minireview | Molecular Biology and Physiology
    Enterobacterial Common Antigen: Synthesis and Function of an Enigmatic Molecule

    The 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...

    Ashutosh K. Rai, Angela M. Mitchell
  • Open Access
    An Essential Membrane Protein Modulates the Proteolysis of LpxC to Control Lipopolysaccharide Synthesis in <span class="named-content genus-species" id="named-content-1">Escherichia coli</span>
    Research Article | Molecular Biology and Physiology
    An Essential Membrane Protein Modulates the Proteolysis of LpxC to Control Lipopolysaccharide Synthesis in Escherichia coli

    The 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...

    Elayne M. Fivenson, Thomas G. Bernhardt
  • Open Access
    YejM Modulates Activity of the YciM/FtsH Protease Complex To Prevent Lethal Accumulation of Lipopolysaccharide
    Research Article | Molecular Biology and Physiology
    YejM Modulates Activity of the YciM/FtsH Protease Complex To Prevent Lethal Accumulation of Lipopolysaccharide

    Gram-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...

    Randi L. Guest, Daniel Samé Guerra, Maria Wissler, Jacqueline Grimm, Thomas J. Silhavy
  • Open Access
    Genetic and Chemical-Genetic Interactions Map Biogenesis and Permeability Determinants of the Outer Membrane of <span class="named-content genus-species" id="named-content-1">Escherichia coli</span>
    Research Article | Molecular Biology and Physiology
    Genetic and Chemical-Genetic Interactions Map Biogenesis and Permeability Determinants of the Outer Membrane of Escherichia coli

    Gram-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...

    Kristina Klobucar, Shawn French, Jean-Philippe Côté, James R. Howes, Eric D. Brown
  • Open Access
    Novel Cassette Assay To Quantify the Outer Membrane Permeability of Five β-Lactams Simultaneously in Carbapenem-Resistant <em>Klebsiella pneumoniae</em> and <em>Enterobacter cloacae</em>
    Research Article | Therapeutics and Prevention
    Novel Cassette Assay To Quantify the Outer Membrane Permeability of Five β-Lactams Simultaneously in Carbapenem-Resistant Klebsiella pneumoniae and Enterobacter cloacae

    Antimicrobial 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...

    Tae Hwan Kim, Xun Tao, Bartolome Moya, Yuanyuan Jiao, Kari B. Basso, Jieqiang Zhou, Yinzhi Lang, Dhruvitkumar S. Sutaria, Alexandre P. Zavascki, Afonso L. Barth, Stephanie M. Reeve, Herbert P. Schweizer, Deanna Deveson Lucas, John D. Boyce, Robert A. Bonomo, Richard E. Lee, Beom Soo Shin, Arnold Louie, George L. Drusano, Jürgen B. Bulitta
  • Open Access
    Sequential Translocation of Polypeptides across the Bacterial Outer Membrane through the Trimeric Autotransporter Pathway
    Research Article | Molecular Biology and Physiology
    Sequential Translocation of Polypeptides across the Bacterial Outer Membrane through the Trimeric Autotransporter Pathway

    Trimeric 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...

    Rakesh Sikdar, Harris D. Bernstein

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