Targeting Membrane Transport Steps in Cell Envelope Assembly

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Principal Investigator: Daniel  Kahne
Organization: HARVARD UNIVERSITY
Fiscal Year: 2024
Award: $726,665
Funding agency: National Institute of Allergy and Infectious Diseases

Project Summary/Abstract
Infections due to Gram-negative bacteria and mycobacterium tuberculosis (Mtb) pose a serious threat to human
health. These organisms produce especially complex cell envelopes consisting of a double layer of membranes
that are essential for survival. This cell envelope also functions as a physical barrier to block entry of many
classes of antibiotics and thereby render them ineffective. This research is directed towards understanding the
structure and function of three protein transporters responsible for cell envelope assembly. Each of these
transporters represents one of the three major transporter families, namely ABC transporters, MOPS
transporters, and RND transporters. To understand how these transporters move their complex glycolipid cargo,
biochemical and structural studies will be undertaken. Intermediates and inhibitors of transport and assembly of
will be characterized structurally, biochemically, and in cells. A better understanding of these proteins’ roles in
cell envelope assembly will lead to new therapies to treat resistant infections.

Terms: <A baumanni><A baumannii><A. baumanni><A. baumannii><A.baumannii><ABC Transport Protein><ABC Transporter Protein><ABC Transporters><ATP-Binding Cassette Transporters><Acinetobacter baumanni><Acinetobacter baumannii><Address><Affinity><Amino Acids><Amino Acyl T RNA Synthetases><Amino Acyl-tRNA Ligases><Amino Acyl-tRNA Synthetases><Aminoacyl Transfer RNA Synthetase><Aminoacyl-tRNA Synthetase><Antibiotic Agents><Antibiotic Drugs><Antibiotics><Assay><Bacteria><Bioassay><Biochemical><Biochemistry><Biogenesis><Biological Assay><Biological Chemistry><Biology><Carrier Proteins><Cell Body><Cell Components><Cell Structure><Cell surface><Cells><Cellular Structures><Collaborations><Complex><Cytoplasm><Data><Development><Disaccharides><Drug resistance><Drugs><E coli><E. coli><Escherichia coli><Face><Family><Genus Mycobacterium><Glycans><Glycolipids><Gram-Negative Bacteria><Health><Human><Impairment><Infection><Lipid A><Lipid Binding><Lipids><Lipopolysaccharides><M tb><M tuberculosis><M. tb><M. tuberculosis><MPPPUP><Maps><Medication><Membrane><Membrane Transport><Methods><Miscellaneous Antibiotic><Modern Man><Molecular Configuration><Molecular Conformation><Molecular Stereochemistry><Monitor><Murein><Mycobacterium><Mycobacterium tuberculosis><Mycolic Acid><Organism><Origin of Life><Pathway interactions><Penetration><Peptidoglycan><Periplasmic Space><Permeability><Pharmaceutical Preparations><Polymers><Polysaccharides><Process><Proteins><Public Health><Pump><Research><Resistance><Role><Side><Structure><Surface><TB therapy><TB treatment><Therapeutic Uses><Toxic effect><Toxicities><Transfer RNA Synthetase><Transmembrane Transport><Transport Protein Gene><Transport Proteins><Transporter Protein><Trehalose><Variant><Variation><Work><aminoacid><aminoacid tRNA ligase><cell assembly><cell envelope><conformation><conformational><conformational state><conformationally><conformations><developmental><drug resistant><drug/agent><faces><facial><improved><inhibitor><lipid bound><living system><membrane structure><mtb><multidisciplinary><muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol><new approaches><new drug treatments><new drugs><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel approaches><novel drug treatments><novel drugs><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel strategies><novel strategy><novel therapeutics><novel therapy><pathway><peptidoglycan precursor lipid II><periplasm><polymer><polymeric><resistance frequency><resistance to Drug><resistant><resistant to Drug><small molecule><social role><structural biology><sugar><tRNA Synthetase><therapeutic agent development><therapeutic development><tool><transport inhibitor><treat M. tuberculosis><treat Mtb><treat Mycobacterium tuberculosis><treat tb><treat tuberculosis><tuberculosis therapy><tuberculosis treatment>