A5016982716- Antibiotic Resistance in Bacteria
- Enzyme Structure and Function
- Bacterial Genetics and Biotechnology
- Drug Transport and Resistance Mechanisms
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Amino Acid Enzymes and Metabolism
- Protein Structure and Dynamics
- Biochemical and Molecular Research
- Antimicrobial Peptides and Activities
- RNA Interference and Gene Delivery
- Carbohydrate Chemistry and Synthesis
- Lipid Membrane Structure and Behavior
- Porphyrin Metabolism and Disorders
- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Trace Elements in Health
- Cancer therapeutics and mechanisms
- Microbial Natural Products and Biosynthesis
- DNA and Nucleic Acid Chemistry
- Bacterial Identification and Susceptibility Testing
- ATP Synthase and ATPases Research
- Selenium in Biological Systems
- Polyamine Metabolism and Applications
Research Complex at Harwell
2016-2025
Rutherford Appleton Laboratory
2016-2025
Imperial College London
2016-2025
Imperial Valley College
2024
Apple (Israel)
2018
Laboratoire de Biologie Physico-Chimique des Protéines Membranaires
2008-2016
Diamond Light Source
2008-2015
University of St Andrews
2002-2011
Aristotle University of Thessaloniki
2007
University of York
2003
Significance ATP-binding cassette (ABC) exporters transport substrates by an alternating access mechanism that is driven ATP binding and hydrolysis. The general a motion from inward to outward state, with different intertwining of the half-transporters in both states. In this study we determined function crystal structure ABC exporter McjD exports antibacterial peptide microcin J25. Our represents novel nucleotide-bound, outward-occluded state. It does not possess subunit shows well-defined...
A lasso peptide takes the spotlight. This review summarizes 30 years of research on microcin J25 and covers everything from its discovery in 1992, through study antimicrobial activity, to most recent application bioengineering.
Capsular polysaccharides (CPSs) are essential virulence determinants of many pathogenic bacteria. Escherichia coli group 1 CPSs provide paradigms for widespread surface polysaccharide assembly systems in Gram-negative In these systems, complex carbohydrate polymers must be exported across the periplasm and outer membrane to cell surface. Group CPS export requires oligomers protein, Wza, translocation membrane. Assembly also depends on Wzc, an inner tyrosine autokinase known regulate...
Obtaining well-ordered crystals is a major hurdle to X-ray structure determination of membrane proteins. To facilitate crystal optimization, we investigated the detergent stability 24 eukaryotic and prokaryotic proteins, predominantly transporters, using fluorescent-based unfolding assay. We have benchmarked required for crystallization in small micelle detergents, as they are statistically more likely lead high-resolution structures. Using this information, been able obtain well-diffracting...
Antibiotic-resistant bacteria, particularly Gram negative species, present significant health care challenges. The permeation of antibiotics through the outer membrane is largely effected by porin superfamily, changes in which contribute to antibiotic resistance. A series resistant E. coli isolates were obtained from a patient during serial treatment with various antibiotics. sequence OmpC changed at three positions giving rise total four variants (denoted OmpC20, OmpC26, OmpC28 and OmpC33,...
Abstract Carbapenem-resistance in Klebsiella pneumoniae (KP) sequence type ST258 is mediated by carbapenemases (e.g. KPC-2) and loss or modification of the major non-selective porins OmpK35 OmpK36. However, mechanism underpinning OmpK36-mediated resistance consequences these changes on pathogenicity remain unknown. By solving crystal structure a clinical OmpK36 variant we provide direct structural evidence pore constriction, di-amino acid (Gly115-Asp116) insertion into loop 3, restricting...
Abstract Bacterial conjugation mediates contact-dependent transfer of DNA from donor to recipient bacteria, thus facilitating the spread virulence and resistance plasmids. Here we describe how variants plasmid-encoded outer membrane (OM) protein TraN cooperate with distinct OM receptors in recipients mediate mating pair stabilization efficient transfer. We show that plasmid pKpQIL ( Klebsiella pneumoniae ) interacts OmpK36, plasmids R100-1 Shigella flexneri pSLT Salmonella Typhimurium)...
Abstract Multidrug resistance-associated protein 2 (MRP2/ABCC2) is a polyspecific efflux transporter of organic anions expressed in hepatocyte canalicular membranes. MRP2 dysfunction, Dubin-Johnson syndrome or by off-target inhibition, for example the uricosuric drug probenecid, elevates circulating bilirubin glucuronide and cause jaundice. Here, we determine cryo-EM structure rat Mrp2 (rMrp2) an autoinhibited state complex with probenecid. The exhibits unusual conformation this class which...
Abstract Conjugation plays a major role in dissemination of antimicrobial resistance genes. Following transfer IncF-like plasmids, recipients become refractory to second wave conjugation with the same plasmid via entry (TraS) and surface (TraT) exclusion mechanisms. Here, we show that TraT from pKpQIL F plasmids (TraT ) exhibits specificity. The cryo-EM structures reveal they oligomerise into decameric champagne bottle cork-like structures, which are anchored outer membrane diacylglycerol...
SbmA is an inner membrane protein of Gram-negative bacteria that involved in the internalization glycopeptides and prokaryotic eukaryotic antimicrobial peptides, as well peptide nucleic acid (PNA) oligomers. The homolog BacA required for development Sinorhizobium meliloti bacteroids within plant cells favors chronic infections with Brucella abortus Mycobacterium tuberculosis mice. Here, we investigated functional features SbmA/BacA using proline-rich Bac7(1-35) a substrate. Circular...
Many pathogenic bacteria utilise sialic acids as an energy source or use them external coating to evade immune detection. As such, that colonise sialylated environments deploy specific transporters mediate import of scavenged acids. Here, we report a substrate-bound 1.95 Å resolution structure and subsequent characterisation SiaT, acid transporter from Proteus mirabilis. SiaT is secondary active the sodium solute symporter (SSS) family, which Na
Article1 September 2017Open Access Source DataTransparent process Structural basis for antibacterial peptide self-immunity by the bacterial ABC transporter McjD Kiran Bountra Department of Life Sciences, Imperial College London, UK Rutherford Appleton Laboratory, Research Complex at Harwell, Oxfordshire, Search more papers this author Gregor Hagelueken Institute Physical and Theoretical Chemistry, University Bonn, Germany Hassanul G Choudhury Valentina Corradi Centre Molecular Simulation...
Article20 September 2018Open Access Transparent process Conformational dynamics of the ABC transporter McjD seen by single-molecule FRET Florence Husada Molecular Microscopy Research Group, Zernike Institute for Advanced Materials, University Groningen, The Netherlands Search more papers this author Kiran Bountra Department Life Sciences, Imperial College London, UK Rutherford Appleton Laboratory, Complex at Harwell, Didcot, Konstantinos Tassis Marijn de Boer Maria Romano Sylvie Rebuffat...
Abstract Super-resolution fluorescence microscopy plays a crucial role in our understanding of cell structure and function by reporting cellular ultrastructure with 20–30 nm resolution. However, this resolution is insufficient to image macro-molecular machinery at work. A path improve under cryogenic conditions. This substantially increases the brightness most fluorophores preserves native much better than chemical fixation. Cryogenic conditions are, however, underutilised because lack...
Mutations in outer membrane porins act synergy with carbapenemase enzymes to increase carbapenem resistance the important nosocomial pathogen, Klebsiella pneumoniae (KP). A key example is a di-amino acid insertion, Glycine-Aspartate (GD), extracellular loop 3 (L3) region of OmpK36 which constricts pore and restricts entry carbapenems into bacterial cell. Here we combined genomic experimental approaches characterise diversity, spread impact different L3 insertion types OmpK36. We identified...
Horizontal gene transfer via conjugation plays a major role in bacterial evolution. In F-like plasmids, efficient DNA is mediated by close association between donor and recipient bacteria. This process, known as mating pair stabilization (MPS), interactions the plasmid-encoded outer membrane (OM) protein TraN chromosomally-encoded OM proteins recipient. We have recently reported existence of 7 sequence types, which are grouped into 4 structural that we named TraNα, TraNβ, TraNγ, TraNδ....
Antibiotic metabolites and antimicrobial peptides mediate competition between bacterial species. Many of them hijack inner outer membrane proteins to enter cells. Sensitivity enteric bacteria multiple peptide antibiotics is controlled by the single protein SbmA. To establish molecular mechanism transport SbmA related BacA, we determined their cryo–electron microscopy structures at 3.2 6 Å local resolution, respectively. The show a previously unknown fold, defining new class secondary...