Novel antibiotics that target essential membrane transporters in pathogenic bacteria
Lead Research Organisation:
University of Cambridge
Department Name: Pharmacology
Abstract
With the growing concerns over the use of antibiotics and the urgent need for novel therapeutics, this project aims to design and synthesise new inhibitors targeting bacterial membrane proteins.
ATP-binding cassette transporters (ABC) are ubiquitous membrane proteins involved in cell viability and drug resistance. MsbA is an ABC transporter native to pathogenic bacteria including E. coli, Salmonella spp., P. aeruginosa, V. cholerae and K. pneumoniae where it has a primary role in the transport of Lipid A in the first stage of lipopolysaccharide biosynthesis of the outer membrane of these pathogens. The synthesis of the outer membrane is vital for the viability of these bacteria and makes this class of bacteria particularly challenging to target with therapeutics. MsbA has been extensively studied biochemically and structurally. It is an essential lipid transporter in many Gram-negative pathogens and is also well recognised as a model ABC multidrug transporter in drug resistance studies. This project will apply a rational design approach to manufacture synthetic peptide inhibitors. Peptides are a newly emerging class of therapeutics that have not yet been developed for bacterial ABC transporters. The design of peptides using the primary sequence of transmembrane domain alpha-helices has the potential to allow for insertion of peptide across the phospholipid bilayer and specific disruption of both the lipid and drug transport activities of MsbA.
Despite having promising medicinal applications, peptide therapeutics are limited by poor stability, membrane permeability and oral bioavailability. The benefits, such as high efficacy, selectivity, low toxicity, and low production costs compared to other biotherapeutics, have encouraged investigations into new methods to overcome the intrinsic limitations of peptides. Peptide stapling is a technique that can constrain peptide sequences into their biologically-active conformations through a chemical brace. This project will aim to develop and identify peptide staples that utilise natural amino acid chemistry and can be further modified for specific cell tagging or tagging to specific uptake pathways to improve peptide accumulation in Gram-negative bacteria. ABC transporters play a large role in multidrug resistance as well as being essential for cell viability. Drugs are often effluxed by native, fast-acting export systems with broad substrate specificity, which therefore significantly contribute to bacterial multidrug resistance. Through identification and characterisation of these peptide inhibitors this project aims to better understand the transport of cytotoxic molecules out of bacteria in the hope of designing a systematic protocol for development of new antibiotics and modulators against multidrug resistant pathogens.
ATP-binding cassette transporters (ABC) are ubiquitous membrane proteins involved in cell viability and drug resistance. MsbA is an ABC transporter native to pathogenic bacteria including E. coli, Salmonella spp., P. aeruginosa, V. cholerae and K. pneumoniae where it has a primary role in the transport of Lipid A in the first stage of lipopolysaccharide biosynthesis of the outer membrane of these pathogens. The synthesis of the outer membrane is vital for the viability of these bacteria and makes this class of bacteria particularly challenging to target with therapeutics. MsbA has been extensively studied biochemically and structurally. It is an essential lipid transporter in many Gram-negative pathogens and is also well recognised as a model ABC multidrug transporter in drug resistance studies. This project will apply a rational design approach to manufacture synthetic peptide inhibitors. Peptides are a newly emerging class of therapeutics that have not yet been developed for bacterial ABC transporters. The design of peptides using the primary sequence of transmembrane domain alpha-helices has the potential to allow for insertion of peptide across the phospholipid bilayer and specific disruption of both the lipid and drug transport activities of MsbA.
Despite having promising medicinal applications, peptide therapeutics are limited by poor stability, membrane permeability and oral bioavailability. The benefits, such as high efficacy, selectivity, low toxicity, and low production costs compared to other biotherapeutics, have encouraged investigations into new methods to overcome the intrinsic limitations of peptides. Peptide stapling is a technique that can constrain peptide sequences into their biologically-active conformations through a chemical brace. This project will aim to develop and identify peptide staples that utilise natural amino acid chemistry and can be further modified for specific cell tagging or tagging to specific uptake pathways to improve peptide accumulation in Gram-negative bacteria. ABC transporters play a large role in multidrug resistance as well as being essential for cell viability. Drugs are often effluxed by native, fast-acting export systems with broad substrate specificity, which therefore significantly contribute to bacterial multidrug resistance. Through identification and characterisation of these peptide inhibitors this project aims to better understand the transport of cytotoxic molecules out of bacteria in the hope of designing a systematic protocol for development of new antibiotics and modulators against multidrug resistant pathogens.
| Description | This work aimed to elucidate the characteristics of inhibition of MsbA and PatAB while introducing novel strategies to target membrane transporters in the ABC superfamily, summarising the state of drug development against these proteins and the available functional techniques to study inhibition. First, extensive characterisation of the interactions of PatAB with its transport substrates revealed two distinct responses to substrate binding. While many of these substrates did not affect the rate of nucleotide hydrolysis, suggesting that nucleotide hydrolysis is always switched on for these substrates, a subclass of substrates including ethidium, propidium and aminocoumarin antibiotics showed strong non-competitive inhibition of hydrolysis both for protein in detergent solution and lipidic nanodiscs. Three models for substrate-protein interaction are presented, including a novel inhibitory antibiotic binding site near the nucleotide-binding domain. This activity appears to be unique for heterodimeric ABC transporter and identification of the inhibitory site might provide a novel specific target to re-sensitise antibiotic resistance of S. pneumoniae infections. Second, this work introduces a novel class of inhibitors specifically targeting MsbA. As MsbA is one of the best-characterised proteins of the ABC superfamily that is essential for cell growth, this ABC transporter is an ideal candidate for inhibitor development. Towards this goal, a library of rationally designed peptide inhibitors was generated from the primary sequence of the transmembrane domain. These peptides were designed to be a-helical membrane spanning synthetic peptides that disrupt helix-helix interactions required for conformational changes. Potent inhibitory activity was observed from a hit peptide in vitro and in vivo on both the lipid transport and small molecule efflux activity of MsbA. Finally, having identified pitfalls and bottlenecks during our inhibitor design process, we developed a novel screening platform combining electrical measurements with MsbA activity in native-like supported lipid bilayers. Using optical, biochemical and electrical measurements we validated the use of PEDOT:PSS electrodes which provide the option for high throughput screening in native-like environments. |
| Exploitation Route | This work aimed to identify a roadmap for designing inhibitors for ABC transporter proteins. Regarding the peptide inhibitors, the outcomes of this work have identified some pitfalls and bottlenecks in this process such as the high occurrence of off-target effects on bacterial membranes when targeting highly hydrophobic regions of the membrane. This work has also identified particular alpha-helices of MsbA that hold more potential for inhibition with synthetic peptides than others suggesting further investigation into their role in protein dimerization. Part of this work has also set up devices for use in screening of inhibitory compounds to control for changes in the energetics and stability of bacterial membranes. Our research on mechanisms of inhibition of MsbA and PatAB, and our successful development of the first-known peptide inhibitors of MsbA open the way to further develop agents that can resensitise drug-efflux-based resistance in pathogenic microorganisms. Therefore, this research is expected to impact the wider development of resistance-breaking pharmaceutical agents and novel methods in medical biotechnology. |
| Sectors | Pharmaceuticals and Medical Biotechnology |
| Title | Biotin-lipid flippase assay |
| Description | Lipid flopping is detected by the movement of the lipid from the external to the internal membrane leaflet. The reduction in the amount of external biotin-PE over time is quantified from the emission of fluorescence-tagged avidin when a quencher in complex with the avidin is displaced by the biotin moiety of the PE. The method provides an alternative for measurements of lipid flopping based on fluorescent lipid analogues, and is published in: Guo D, Singh H, Shimoyama A, Guffick C, Tang Y, Rowe SM, Noel T, Spring DR, Fukase K, van Veen HW. Energetics of lipid transport by the ABC transporter MsbA is lipid dependent. Commun Biol. 2021 Dec 9;4(1):1379. doi: 10.1038/s42003-021-02902-8. PubMed PMID: 34887543; PubMed Central PMCID: PMC8660845. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | By using biotinylated lipids rather than fluorescent NBD-labelled lipid analogues, we were able for the first time to measure lipid transport by the ABC multidrug transporter MsbA. As the NBD moiety is structurally similar to fluorescent cytotoxic agents, the NBD-lipids might be recognised as drug analogues rather than lipid analogues. |
| Title | Electrophysiological measurements on ABC transporter MsbA |
| Description | Application of electrochemical impedance spectroscopy (EIS) to monitor ion flow through MsbA proteins in response to ATP hydrolysis |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2023 |
| Provided To Others? | Yes |
| Impact | As the threat of antibiotic resistance increases, there is a particular focus on developing antimicrobials against pathogenic bacteria whose multidrug resistance is especially entrenched and concerning. One such target for novel antimicrobials is the ATP-binding cassette (ABC) transporter MsbA that is present in the plasma membrane of Gram-negative pathogenic bacteria where it is fundamental to the survival of these bacteria. Supported lipid bilayers (SLBs) are useful in monitoring membrane protein structure and function since they can be integrated with a variety of optical, biochemical, and electrochemical techniques. Here, we form SLBs containing Escherichia coli MsbA and use atomic force microscopy (AFM) and structured illumination microscopy (SIM) as high-resolution microscopy techniques to study the integrity of the SLBs and incorporated MsbA proteins. We then integrate these SLBs on microelectrode arrays (MEA) based on the conducting polymer poly(3,4-ethylenedioxy-thiophene) poly(styrene sulfonate) (PEDOT:PSS) using electrochemical impedance spectroscopy (EIS) to monitor ion flow through MsbA proteins in response to ATP hydrolysis. These EIS measurements can be correlated with the biochemical detection of MsbA-ATPase activity. To show the potential of this SLB approach, we observe not only the activity of wild-type MsbA but also the activity of two previously characterized mutants along with quinoline-based MsbA inhibitor G907 to show that EIS systems can detect changes in ABC transporter activity. Our work combines a multitude of techniques to thoroughly investigate MsbA in lipid bilayers as well as the effects of potential inhibitors of this protein. We envisage that this platform will facilitate the development of next-generation antimicrobials that inhibit MsbA or other essential membrane transporters in microorganisms. |
| URL | https://pubs.acs.org/doi/10.1021/acsami.2c21556 |
| Title | Research data supporting "Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae" |
| Description | The bacterial heterodimeric ATP-binding cassette (ABC) multidrug exporter PatAB has a critical role in conferring antibiotic resistance in multidrug-resistant infections by Streptococcus pneumoniae. As with other heterodimeric ABC exporters, PatAB contains two transmembrane domains that form a drug translocation pathway for efflux and two nucleotide-binding domains that bind ATP, one of which is hydrolysed during transport. The structural and functional elements in heterodimeric ABC multidrug exporters that determine interactions with drugs and couple drug binding to nucleotide hydrolysis are not fully understood. Here, we used mass spectrometry techniques to determine the subunit stoichiometry in PatAB in our lactococcal expression system and investigate locations of drug binding using the fluorescent drug-mimetic azido-ethidium. Surprisingly, our analyses of azido-ethidium-labelled PatAB peptides point to ethidium binding in PatA nucleotide-binding domain, with the azido moiety crosslinked to residue Q521 in the H-like loop of the degenerate nucleotide-binding site. Investigation into this compound and residue's role in nucleotide hydrolysis pointed to a reduction in the activity for a Q521A mutant and ethidium-dependent inhibition in both mutant and wild type. Most transported drugs did not stimulate or inhibit nucleotide hydrolysis of PatAB in detergent solution or lipidic nanodiscs. However, further examples for ethidium-like inhibition were found with propidium, novobiocin and coumermycin A1, which all inhibit nucleotide hydrolysis by a non-competitive mechanism. These data cast light on potential mechanisms by which drugs can regulate nucleotide hydrolysis by PatAB, which might involve a novel drug binding site near the nucleotide-binding domains. The research data in this dataset record support the publication by Guffick et al. in FEBS J. and refer to the figures that are incorporated in the paper, and the DNA and protein sequences under study. Descriptions of the experimental details and statistical analyses are included in the Materials and Methods and figure legends of the paper. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2022 |
| Provided To Others? | Yes |
| Impact | The research data in this dataset record support the publication by Guffick et al. in FEBS J. and refer to the figures that are incorporated in the paper, and the DNA and protein sequences under study. |
| URL | https://www.repository.cam.ac.uk/handle/1810/332942 |
| Description | Collaboration with Dr Keiko Shinoda |
| Organisation | University of Tokyo |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | I collaborate with Dr Shinoda who performs molecular dynamics simulations with protein structures of the multidrug transporters under study in the VanVeen group. We deliver complementary functional data of these membrane transporters. Together these MD simulations and functional data reveal how these transporters operate. |
| Collaborator Contribution | Dr Shinoda has been responsible for molecular dynamics (MD) simulations in our project on the MATE transporter NorM-VC from Vibrio cholerae. She is also involved in the MD simulations in other ongoing research projects in the VanVeen research group. In the University of Tokyo, Dr Shinoda has access to the high-speed supercomputers and software required for the MD simulations study. |
| Impact | Publications including Raturi et al Commun Biol 2021 and current studies on MATE transporters as well as MFS and ABC transporters. |
| Start Year | 2019 |
| Description | Collaboration with Prof Robinson at University of Oxford |
| Organisation | University of Oxford |
| Department | Department of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My research team generates the samples of purified protein in detergent solution or in lipidic nanodiscs. |
| Collaborator Contribution | The Robinson team applies native mass spectrometry on our protein samples to analyse the subunit composition as well as lipid and drug binding in the protein complexes. |
| Impact | Guffick C, Hsieh PY, Ali A, Shi W, Howard J, Chinthapalli DK, Kong AC, Salaa I, Crouch LI, Ansbro MR, Isaacson SC, Singh H, Barrera NP, Nair AV, Robinson CV, Deery MJ, van Veen HW. Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae. FEBS J. 2022 Jan 23;. doi: 10.1111/febs.16366. [Epub ahead of print] PubMed PMID: 35066976. |
| Start Year | 2020 |
| Description | Collaboration with Professor David Spring |
| Organisation | University of Cambridge |
| Department | Department of Chemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This PhD research receives input from the Department of Pharmacology in the areas of pharmacology, biochemistry and structure-function relationships in ABC multidrug transporters. |
| Collaborator Contribution | This PhD research receives input from the Department of Chemistry in the chemical synthesis of peptide inhibitors and organic inhibitors of ABC multidrug transporters |
| Impact | A fair number of potential peptide inhibitors have been synthesized as well as quinoline compounds with known inhibitor activity. A number of these peptides were found to be active as inhibitors of multidrug efflux activity in cells and in proteoliposomes containing purified transport proteins. |
| Start Year | 2018 |
| Description | Collaboration with Professor Róisín Owens |
| Organisation | University of Cambridge |
| Department | Department of Chemical Engineering and Biotechnology |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This PhD research receives input from the Department of Pharmacology in the areas of pharmacology, biochemistry and structure-function relationships in ABC multidrug transporters including the preparation of reconstituted protein samples. |
| Collaborator Contribution | This PhD research receives input from the Department of Chemical Engineering and Biotechnology in the manufacture and assembly of devices for the study of ABC multidrug transporter function and inhibition. |
| Impact | ABC transporters have been successfully set up and explored on the device system that has allowed for further understanding of transporter activity and a manuscript is in preparation. |
| Start Year | 2020 |
| Description | Synthesis of biotinylated lipids |
| Organisation | Osaka University |
| Department | Graduate School of Science |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Dr Atsushi Shimoyama and Prof Koichi Fukase, Department of Chemistry, Graduate School of Science, Osaka University |
| Collaborator Contribution | Dr Shimoyama and Prof Fukase have chemically synthesized biotinylated lipids that we use in lipid transport assays. |
| Impact | We have successfully used the synthetic lipids in transport assays. |
| Start Year | 2018 |
| Description | BBSRC DTP Symposium, Cambridge; Virtual event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Postgraduate students |
| Results and Impact | Poster presentation by C. Guffick 'Developing Transmembrane Helix Mimic Peptides to Target Essential Bacterial Lipid and Multidrug Transporter MsbA' Authors: Guffick, C., Rowe, S. M., Pfitzner, S., Spring, D., van Veen, H. W. |
| Year(s) Of Engagement Activity | 2020 |
| Description | Biochemical Society Conference - Molecular Mechanism of Membrane Proteins |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Poster Presentation by Y. Tang at Biochemical Society meeting in Birmingham Title: Energetics of lipid transport by the ABC transporter MsbA is lipid dependent Authors: Tang, Y., Guo, D., Singh, H., Shimoyama, A., Guffick, C., Rowe, S.M., Noel, T., Spring, D.R., Fukase, K., Van Veen, H.W. |
| Year(s) Of Engagement Activity | 2023 |
| Description | Cambridge Infectious Diseases Annual Symposium, Cambridge, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Study participants or study members |
| Results and Impact | Poster presentation by C. Guffick 'Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae' Authors: Guffick, C., Hsieh, P. Y., Ali, A., Shi, W., Howard, J., Chinthapalli, D. K., Kong, A. C., Singh, H., Salaa, I., Robinson, C. V., Deery, M. J. & van Veen, H. W. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.infectiousdisease.cam.ac.uk/events/cid-annual-meeting-of-minds-1 |
| Description | EMBO Workshop: Membrane transporters as essential elements of cellular function and homeostasis + Mechanical Sensing & Ion Channels, Chania, Greece |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | Poster presentation by C. Guffick: 'Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae' Authors: Guffick, C., Hsieh, P. Y., Ali, A., Shi, W., Howard, J., Chinthapalli, D. K., Kong, A. C., Singh, H., Salaa, I., Robinson, C. V., Deery, M. J. & van Veen, H. W. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://meetings.embo.org/event/21-membrane-transporters |
| Description | Gordon Research Conference, "Multi-Drug Efflux Systems: Targerting the Mechanisms and Regulation of Transporters for Advancing Health During a Pandemic', Galveston, Texas, US |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | Poster presentation: "Drug-dependent inhibi/on of nucleo/de hydrolysis in the heterodimeric ABC mul/drug transporter PatAB from Streptococcus pneumoniae". Authors: Guffick, C., Hsieh, P. Y., Ali, A., Shi, W., Howard, J., Chinthapalli, D. K., Kong, A. C., Singh, H., Salaa, I., Robinson, C. V., Deery, M. J. & van Veen, H. W. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.grc.org/multi-drug-efflux-systems-conference/2023/ |
| Description | Gordon Research Seminar, 'Multi-Drug Efflux Systems: Insights into the Strucutre and Function of Multi-Drug Efflux Systems for Novel Applications in Global Public Health', Galveston, Texas, US |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | Discussion Leader, Selected Speaker and Poster Presentation by C. Guffick: "A biosensor for multi-modal characterisation of an essential ABC transporter for next- generation antibiotics" Authors: Guffick, C., Bali. K., Mccoy, R., Lu, Z. H., Kaminski, C., Mela, I., Owens, R., van Veen, H. W. |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://www.grc.org/multi-drug-efflux-systems-grs-conference/2023/ |
| Description | Invited lecture at Hokkaido University, Japan |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Van Veen, H.W. (2019) Studies on the Lipid-A transporter MsbA and its homologue LmrA. Presentation on our current research at Hokkaido University. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited lecture at Tokyo Institute of Technology, Japan |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Van Veen, H.W. (2019) Studies on the Lipid-A transporter MsbA and its homologue LmrA. Presentations on our current research at Tokyo Institute of Technology. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited lecture at the University of Osaka, Japan |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Van Veen, H.W. (2019) Studies on the Lipid-A transporter MsbA and its homologue LmrA. Presentations on our current research at the University of Osaka. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited lecture at the University of Tokyo, Japan |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Van Veen, H.W. (2019) Studies on the Lipid-A transporter MsbA and its homologue LmrA. Presentation on our current research at the University of Tokyo. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Invited talk at 8th FEBS Special Meeting on ABC Proteins |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited talk at 8th FEBS Special Meeting on ABC Proteins in Innsbruck, Austria from 2 to 7 March 2020 |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://abc2020.febsevents.org/ |
| Description | Invited talk at University of Oxford |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Invited talk by Hendrik van Veen at the Department of Pharmacology at the University of Oxford |
| Year(s) Of Engagement Activity | 2023 |
| URL | https://talks.ox.ac.uk/talks/persons/id/933c3aeb-7711-4338-8e84-17359038e0e3 |
| Description | Inviteted lecture at the University of Kyoto, Japan |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Van Veen, H.W. (2019) Studies on the Lipid-A transporter MsbA and its homologue LmrA. Presentation on our current research at the University of Kyoto. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Student talk at University of Leeds |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Postgraduate students |
| Results and Impact | Charlotte Guffick gave a presentation on her research at the University of Leeds in the "ABC UK meeting" |
| Year(s) Of Engagement Activity | 2019 |
| Description | TransCure Final Conference, Bern, Switzerland |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Study participants or study members |
| Results and Impact | selected speaker and poster presentation by C. Guffick 'Drug-dependent inhibition of nucleotide hydrolysis in the heterodimeric ABC multidrug transporter PatAB from Streptococcus pneumoniae' Authors; Guffick, C., Hsieh, P. Y., Ali, A., Shi, W., Howard, J., Chinthapalli, D. K., Kong, A. C., Singh, H., Salaa, I., Robinson, C. V., Deery, M. J. & van Veen, H. W. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.nccr-transcure.ch/events/final-conference |
| Description | WAAW ECR Conference, 'Multidisciplinary Approaches to AMR', University of Oxford, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Study participants or study members |
| Results and Impact | flash talk & poster presentation by C. Guffick Authors: Guffick, C., Rowe, S. M., Chinthapalli, D. K., Pfitzner, S., Robinson, C. V., Spring, D., van Veen, H. W. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.ineosoxford.ox.ac.uk/events-outreach/multidisciplinary-approaches-to-amr |