A5031594507- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Drug Transport and Resistance Mechanisms
- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Salmonella and Campylobacter epidemiology
- Bacteriophages and microbial interactions
- Escherichia coli research studies
- Clostridium difficile and Clostridium perfringens research
- Mass Spectrometry Techniques and Applications
- Tuberculosis Research and Epidemiology
- Coordination Chemistry and Organometallics
- Vibrio bacteria research studies
- Trace Elements in Health
- Bacterial Infections and Vaccines
- Fuel Cells and Related Materials
- Genomics and Phylogenetic Studies
- Lipid Membrane Structure and Behavior
- Chemical Reactions and Isotopes
- Nicotinic Acetylcholine Receptors Study
- Streptococcal Infections and Treatments
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Pneumonia and Respiratory Infections
- Chemical Synthesis and Analysis
University of Essex
2016-2024
University of Birmingham
2013-2020
Colchester Institute
2017
University of Oxford
2008-2015
Clarendon College
2012
Pontificia Universidad Católica de Chile
2010
University of Bristol
2010
University of Cambridge
2004-2008
Institut de Biologie et de Chimie des Protéines
2004
Université Claude Bernard Lyon 1
2004
The incidence of multidrug-resistant bacterial infections is increasing globally and the need to understand underlying mechanisms paramount discover new therapeutics. efflux pumps Gram-negative bacteria have a broad substrate range transport antibiotics out bacterium, conferring intrinsic multidrug resistance (MDR). genomes pre- posttherapy MDR clinical isolates Salmonella Typhimurium from patient that failed antibacterial therapy died were sequenced. In isolate we identified novel G288D...
Drugs and certain proteins are transported across the membranes of Gram-negative bacteria by energy-activated pumps. The outer membrane component these pumps is a channel that opens from sealed resting state during transport process. We describe two crystal structures Escherichia coli protein TolC in its partially open state. Opening accompanied exposure three shallow intraprotomer grooves trimer, where our mutagenesis data identify contact point with periplasmic drug efflux pump, AcrA....
Abstract Lipopolysaccharide (LPS) O-antigen (O-Ag) is known to limit antibody binding surface antigens, although the relationship between antibody, O-Ag and other outer-membrane antigens poorly understood. Here we report, immunization with trimeric porin OmpD from Salmonella Typhimurium (STmOmpD) protects against infection. Atomistic molecular dynamics simulations indicate this because trimers generate footprints within layer sufficiently sized for a single IgG Fab access. While STmOmpD...
Acinetobacter are generally soil-dwelling organisms that can also cause serious human infections. A. baumannii is one of the most common causative agents infections and often multidrug resistant. However, an additional 25 species within genus have been associated with infection. encodes six resistance nodulation division (RND) efflux pumps, clinically relevant class pumps for antibiotic export, but distribution types RND across currently unknown. Sixty-four making up were searched systems...
In Gram‐negative bacteria, drug resistance is due in part to the activity of transmembrane efflux‐pumps, which are composed three types proteins. A representative pump from Escherichia coli an assembly trimeric outer‐membrane protein TolC, allosteric channel, inner‐membrane proton‐antiporter AcrB, and periplasmic protein, AcrA. The displaces drugs vectorially bacterium using proton electrochemical force. Crystal structures available for TolC AcrB E. , AcrA homologue MexA Pseudomonas...
Gram-negative bacteria utilize specialized machinery to translocate drugs and protein toxins across the inner outer membranes, consisting of a tripartite complex composed an membrane secondary or primary active transporter (IMP), periplasmic fusion protein, channel. We have investigated assembly function MacAB/TolC system that confers resistance macrolides in Escherichia coli. The MacA not only stabilizes by interacting with both MacB TolC, but also has role regulating MacB, apparently...
Here we examined the gas-phase structures of two tetrameric membrane protein complexes by ion mobility mass spectrometry. The collision cross sections measured for channel are in accord with a compact configuration subunits, suggesting that native-like structure can be preserved under harsh activation conditions required to release it from detergent micelle into gas phase. We also found quaternary transporter, which has fewer transmembrane subunits than channel, is less stable once stripped...
Abstract Antibiotic resistance is a pressing healthcare challenge and mediated by various mechanisms, including the active export of drugs via multidrug efflux systems, which prevent drug accumulation within cell. Here, we studied how Salmonella evolved to two key antibiotics, cefotaxime azithromycin, when grown planktonically or as biofilm. Resistance both emerged in conditions was associated with different substitutions efflux-associated transporter, AcrB. Azithromycin exposure selected...
The multiple transferable resistance (mTR) pump from Neisseria gonorrhoeae MtrCDE multidrug is assembled the inner and outer membrane proteins MtrD MtrE periplasmic fusion protein MtrC. Previously we established that while there a weak interaction of MtrE, MtrC binds with relatively high affinity to both MtrE. conferred antibiotic only when it was expressed MtrC, suggesting these form functional tripartite complex in which bridges Furthermore, demonstrated interacts an intraprotomer groove...
The Gram-negative outer-membrane envelops the bacterium and functions as a permeability barrier against antibiotics, detergents, environmental stresses. Some virulence factors serve to maintain integrity of outer membrane, including DolP (formerly YraP) protein unresolved structure function. Here, we reveal is lipoprotein functionally conserved amongst bacteria that loss increases membrane fluidity. We present NMR solution for Escherichia coli DolP, which composed two BON domains form an...
Summary The MtrCDE multidrug pump, from N eisseria gonorrhoeae , is assembled the inner and outer membrane proteins MtrD MtrE which are connected by periplasmic fusion protein MtrC . Although it clear that delivers drugs to channel of remains unclear how drug delivery opening connected. We used a vancomycin sensitivity assay test for channel. Cells expressing or ‐ E 434 K were insensitive vancomycin; but became moderately highly sensitive respectively, when coexpressed with suggesting...
The multi-protein β-barrel assembly machine (BAM) of Escherichia coli is responsible for the folding and insertion containing integral outer membrane proteins (OMPs) into bacterial membrane. An essential component this complex BamA protein, which binds unfolded precursors via five polypeptide transport-associated (POTRA) domains in its N-terminus. C-terminus contains a domain, tethers to also thought be involved OMP insertion. Here we mutagenize using linker scanning mutagenesis demonstrate...
Active efflux due to tripartite RND pumps is an important mechanism of clinically relevant antibiotic resistance in Gram-negative bacteria. These are also essential for pathogens cause infection and form biofilms. They consist inner membrane transporter; a periplasmic adaptor protein (PAP), outer channel. The role PAPs assembly, the identities specific residues involved PAP-RND binding, remain poorly understood. Using recent high-resolution structures, four 3D sites binding within each PAP...
Salmonella is an important genus of Gram-negative pathogens, treatment which has become problematic due to increases in antimicrobial resistance. This partly attributable the overexpression tripartite efflux pumps, particularly constitutively expressed AcrAB-TolC. Despite its clinical importance, structure AcrB transporter remained unknown to-date, with much our structural understanding coming from Escherichia coli orthologue. Here, by taking advantage styrene maleic acid (SMA) technology...
Morbilliviruses infect a broad range of mammalian hosts, including ruminants, carnivores, and humans. The recent eradication rinderpest virus (RPV) the active campaigns for human-specific measles (MeV) have raised significant concerns that remaining morbilliviruses may emerge in so-called vacated ecological niches. Seeking to assess zoonotic potential nonhuman within human populations, we found peste des petits ruminants (PPRV)-the small-ruminant morbillivirus-is restricted at point entry...