Browsing by Author "Kahne, Daniel"
Now showing items 1-20 of 35
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Advances in Phage-Assisted Continuous Evolution and Application to Overcoming Bioinsecticide Resistance
Badran, Ahmed (2016-05-20)The Bacillus thuringiensis δ-endotoxins (Bt toxins) are widely used insecticidal proteins in engineered crops that provide agricultural, economic, and environmental benefits, constituting a substantial and increasingly ... -
Assembly and Regulation of the Lipopolysaccharide Transporter
Freinkman, Elizaveta (2013-02-20)The hallmark of Gram-negative bacteria is the presence of an outer membrane (OM) surrounding the cytoplasmic membrane (here called the inner membrane [IM]) and the cell wall. The OM is a unique asymmetric bilayer with an ... -
Biochemical and Crystallographic Studies of the Escherichia Coli β-Barrel Assembly Machine
Westwood, David (2016-09-01)Bacteria have developed resistance mechanisms to every class of antibiotics that has been created and combating the rise of multidrug-resistant bacteria—a major threat to public health—requires the continual development ... -
Cell-Based Discovery Methods Furnish New Compounds Effective Against Gram-Negative Bacteria
Baidin, Vadim (2016-07-20)Bacterial resistance to antibiotics inevitably results from their clinical use, and we have to continuously develop new antibiotics to stay ahead in this biological arms race. It is particularly important and challenging ... -
D-Amino Acids Indirectly Inhibit Biofilm Formation in Bacillus subtilis by Interfering with Protein Synthesis
Leiman, Sara A; May, J. M.; Lebar, M. D.; Kahne, Daniel; Kolter, R.; Losick, Richard M. (American Society for Microbiology, 2013)The soil bacterium Bacillus subtilis forms biofilms on surfaces and at air-liquid interfaces. It was previously reported that these biofilms disassemble late in their life cycle and that conditioned medium from late-stage ... -
Decoupling catalytic activity from biological function of the ATPase that powers lipopolysaccharide transport
Sherman, David Joseph; Lazarus, Michael B.; Murphy, Lea; Liu, Charles Xin; Kahne, Suzanne Walker; Ruiz, Natividad; Kahne, Daniel (Proceedings of the National Academy of Sciences, 2014)Gram-negative bacteria contain an unusual outer membrane that prevents the entry of most currently available antibiotics. This membrane contains a complex glycolipid, LPS, on the exterior. It is not understood how such a ... -
Detection of Lipid-Linked Peptidoglycan Precursors by Exploiting an Unexpected Transpeptidase Reaction
Qiao, Yuan; Lebar, Matthew D.; Schirner, Kathrin; Schaefer, Kaitlin; Tsukamoto, Hirokazu; Kahne, Daniel; Walker, Suzanne (American Chemical Society, 2014)Penicillin-binding proteins (PBPs) are involved in the synthesis and remodeling of bacterial peptidoglycan (PG). Staphylococcus aureus expresses four PBPs. Genetic studies in S. aureus have implicated PBP4 in the formation ... -
Directed Evolution and Engineering of CRISPR-Associated Nucleases
Davis, Kevin Michael (2016-09-12)CRISPR-Cas systems provide prokaryotes with a remarkable mechanism for adaptive immunity, and recent efforts to understand these systems have provided tremendous insight into the complex nature of these systems. Despite ... -
Discovery and Characterization of the Cylindrocyclophane Biosynthetic Pathway
Nakamura, Hitomi (2016-05-17)Nature constructs structurally diverse, bioactive molecules using enzymes. Many enzymes catalyze synthetically challenging reactions under mild, physiological conditions. Consequently, they have long been a source of ... -
The Escherichia coli Lpt Transenvelope Protein Complex for Lipopolysaccharide Export Is Assembled via Conserved Structurally Homologous Domains
Villa, R.; Martorana, A. M.; Okuda, S.; Gourlay, L. J.; Nardini, M.; Sperandeo, P.; Deho, G.; Bolognesi, M.; Kahne, Daniel; Polissi, A. (American Society for Microbiology, 2013)Lipopolysaccharide is a major glycolipid component in the outer leaflet of the outer membrane (OM), a peculiar permeability barrier of Gram-negative bacteria that prevents many toxic compounds from entering the cell. ... -
Genetics and Regulation of Bacterial Biofilms
Leiman, Sara (2015-03-24)Bacterial biofilm formation, the construction of dense, protective, multicellular communities, is a widely conserved behavior. In some bacteria, such as the Gram-positive model organism Bacillus subtilis, the genetics ... -
Identification and Characterization of Intermediates during Folding on the β-Barrel Assembly Machine in Escherichia coli
Xue, Mingyu (2014-06-06)β-barrel membrane proteins play important structural and functional roles in Gram negative bacteria and in mitochondria and chloroplasts of eukaryotes. A conserved machine is responsible for the folding and insertion of ... -
Identification of Residues in the Lipopolysaccharide ABC Transporter That Coordinate ATPase Activity with Extractor Function
Simpson, Brent W.; Owens, Tristan W.; Orabella, Matthew J.; Davis, Rebecca M.; May, Janine M.; Trauger, Sunia A.; Kahne, Daniel; Ruiz, Natividad (American Society for Microbiology, 2016)ABSTRACT The surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS), creating a permeability barrier against toxic molecules, including many antimicrobials. To assemble LPS on their surface, ... -
Identifying targets for potentiators in S. aureus using chemical genetic approaches
Rajagopal, Mithila (2016-09-29)Staphylococcus aureus is a highly feared Gram-positive pathogen. The rise in antibiotic resistance has made S. aureus infections intractable. To find new ways to treat S. aureus infections, it is important to understand ... -
Inhibition of the βbarrel assembly machine by a peptide that binds BamD
Hagan, Christine Lepicier; Wzorek, Joseph Stanley; Kahne, Daniel (Proceedings of the National Academy of Sciences, 2015)The protein complex that assembles integral membrane β-barrel proteins in the outer membranes of Gram-negative bacteria is an attractive target in the development of new antibiotics. This complex, the β-barrel assembly ... -
Late-Stage Fluorination With 19F− and 18F− via Concerted Nucleophilic Aromatic Substitution
Neumann, Constanze N. (2016-09-09)The formation of C–F bonds has long been considered a challenging transformation and C–F bonds commonly had to be formed early on in a synthetic sequence towards complex organofluorides. Late-stage fluorination reactions ... -
Lipopolysaccharide transport to the cell surface: biosynthesis and extraction from the inner membrane
Simpson, Brent W.; May, Janine Margaret; Sherman, David Joseph; Kahne, Daniel; Ruiz, Natividad (The Royal Society, 2015)The cell surface of most Gram-negative bacteria is covered with lipopolysaccharide (LPS). The network of charges and sugars provided by the dense packing of LPS molecules in the outer leaflet of the outer membrane interferes ... -
Lipopolysaccharide transport to the cell surface: periplasmic transport and assembly into the outer membrane
May, Janine Margaret; Sherman, David Joseph; Simpson, Brent W.; Ruiz, Natividad; Kahne, Daniel (The Royal Society, 2015)Gram-negative bacteria possess an outer membrane (OM) containing lipopolysaccharide (LPS). Proper assembly of the OM not only prevents certain antibiotics from entering the cell, but also allows others to be pumped out. ... -
Lipoprotein Activators Stimulate Escherichia coli Penicillin-Binding Proteins by Different Mechanisms
Lupoli, Tania J.; Lebar, Matthew; Markovski, Monica; Bernhardt, Thomas G.; Kahne, Daniel; Kahne, Suzanne Walker (American Chemical Society (ACS), 2014)In Escherichia coli, the bifunctional penicillin-binding proteins (PBPs), PBP1A and PBP1B, play critical roles in the final stage of peptidoglycan (PG) biosynthesis. These synthetic enzymes each possess a PG glycosyltransferase ... -
A new antibiotic traps lipopolysaccharide in its intermembrane transporter
Pahil, Karanbir S.; Gilman, Morgan S. A.; Baidin, Vadim; Clairfeuille, Thomas; Mattei, Patrizio; Bieniossek, Christoph; Dey, Fabian; Muri, Dieter; Baettig, Remo; Lobritz, Michael; Bradley, Kenneth; Kruse, Andrew C.; Kahne, Daniel (Springer Science and Business Media LLC, 2024-01-03)Gram-negative bacteria are extraordinarily difficult to kill because their cytoplasmic membrane is surrounded by an outer membrane that blocks the entry of most antibiotics. The impenetrable nature of the outer membrane ...