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Research interests

I lead a research group studying antimicrobial drug resistance (AMR) in bacteria. We use molecular genetics, biochemistry and functional genomics techniques to identify and characterise AMR mechanisms in key human pathogens, their mobilisation, and their control. We then use this information to combat the problem of AMR by developing interdisciplinary research collaborations. 

Our current basic work aims to characterize multi-drug resistance mechanisms in non-fermenting Gram-negative bacteria, particularly Stenotrophomonas maltophilia and in the Enterobacterales, particularly Escherichia coli and Klebsiella pneumoniae. We have studied mechanisms of β-lactam and β-lactam/β-lactamase inhibitor resistance (e.g. Calvopiña et al., (2017) Molecular Microbiology; Dulyayangkul et al., (2020a) Antimicrob Agents ChemotherDulyayangkul et al., (2020b) Antimicrob Agents Chemother; Calvopiña et al., (2020) Molecular Microbiology; Takebayashi et al., (2021) J Antimicrob Chemother; Alzayn et al., (2021) Antimicrob Agents Chemother)aminoglycoside resistance (e.g. Calvopiña et al., (2020) Antimicrob Agents Chemother; Dulyayangkul et al., (2021) Front Microbiol), polymyxin resistance (e.g. Cheung et al., (2020) Antimicrob Agents Chemother) and fluoroquinolone resistance (e.g. Wan nur Ismah et al., (2018) J Antimicrob Chemother; Dulyayangkul et al., (2020c) Antimicrob Agents Chemother).

We have collaborated with chemists and structural biologists to develop β-lactamase inhibitors (e.g. Brem et al., (2014) Nature Chemistry; Brem et al., (2016) Nature Communications; Brem et al., (2021) Nature Chemistry), and we are also part of Bristol University's "Silent Pharmacy" consortium led by Dr Andy Bailey (Biological Sciences) and are working in collaboration with chemists, biochemists and mycologists to identify novel antibiotics from fungi.

We have pioneered proteomics-based technologies for the identification of AMR proteins in clinical samples and we are pioneering the use of proteomics to improve the ability of whole genome sequencing to predict antimicrobial susceptiblity (e.g. Wan Nur Ismah et al., (2018) Antimicrob Agents Chemother). We have helped investigate the potential for sensing AMR via volotile profiling (e.g. Smart et al., (2019) J Pharm Biomed Anal; Hewett et al., (2020) Antibiotics). We are also involved in a project led by Physicist Dr Massimo Antognozzi (University of Bristol) to develop novel sensors that can rapidly determine antimicrobial susceptibility in individual bacteria from clinical samples. This project received a global Longitude Prize Discovery Award and has spun out a company, Vitamica Ltd. 

We lead the One Health Selection and Transmission of Antimicrobial Resistance (OH-STAR) consortium. Working with Prof Alasdair MacGowan and Drs Maha Albur and Fergus Hamilton (North Bristol NHS Trust) and Drs Philip Williams and Martin Williams (University Hospitals Bristol & Weston NHS Foundation Trust), we are using whole genome sequencing to survey urinary E. coli and all Gram-negatives from bloodstream infection (e.g. Findlay et al., (2020) J Antimicrob Chemother). Our aims include monitoring ecological shifts resulting from local prescribing policy changes, informing empiric prescribing and IV/oral switch for sepsis, and understanding the transmission and selection of resistance in a clinical setting (e.g. Cheung et al., (2021) Antimicrob Agents Chemother).

Working with Prof Alastair Hay (Population Health Sciences) we aim to identify how changes in prescribing practice in primary care can be used to alter the prevalence of AMR infections in humans (e.g. Hammond et al., (2020) PLOS One) 

Working with Prof Kristen Reyher (Bristol Vet School), we aim to (1) define the environmental and management factors that influence acquisition and selection of AMR bacteria in dairy cattle (e.g. Schubert et al., (2021) Appl Environ Microbioland in dogs and zoo animals and (2) to identify whether AMR bacteria from these animals impacts on AMR in human infections (e.g. Alzayn et al., (2020) J Antimicrob Chemother; Findlay et al., (2020) Appl Environ Microbiol; Mounsey et al., (2021) J Antimicrob Chemother)

We lead the One Health Drivers of Antibacterial Resistance in Thailand (OH-DART) consortium. Working with colleagues at the Universities of Exeter and Bath, Mahidol University, Chulabhorn Research Institute and the NERC Center for Ecology and Hydrology, our consortium's aim is to define and prioritise the drivers of antibacterial drug resistance in humans in the community in Thailand taking a multi-disciplinary approach. So far, we have modelled the impact of the current Thai 5-year national plan on AMR reduction (Booton et al., (2021) One Health). 

We also contribute to the FARMS-SAFE consortium led by Prof Kristen Reyher to work alongside colleagues at the University of La Plata to survey AMR and antimicrobial usage and identify the drivers of AMR in Argentinian farming systems.

As well as directing these core research activities, I lead the Bristol AMR interdisciplinary research network, funded by the Wellcome Trust, which aims to promote, facilitate and bring together AMR research from across the University of Bristol.

I am PI and Academic Lead for the Medical Research Foundation-funded National PhD Training Programme in AMR Research, which will provide 30 fully-funded 4-year, interdisciplinary PhD studentships and will fund cohort building and knowledge exchange events for up to 175 additional PhD students working on AMR related projects from all disciplines and all UK institutions.

Current Grant Funding

  • 01/20-01/23: MRC CARP Award (CoI)
  • 08/19-06/23: BBSRC/DoHSC Consortium Grant (CoI)
  • 09/18-11/21: Wellcome Trust Strategic Award (PI)
  • 05/18-11/21: MRC/DoHSC Consortium Grant (PI)
  • 10/17-02/24: Medical Research Foundation DTP (PI)
  • 09/16-12/21: MRC/BBSRC Consortium Grant (CoI)

Research Team

  • Maryam Alzayn, BSc (Tabuk), MSc (Bangor) - PhD Student
  • Nour Alhusein, BSc (Damascus), PhD (Bath) - Senior Research Associate (MRC Funded)
  • Thomas Beavis - MSci Student
  • Ross Booton, MSci (Bath), PhD (Sheffield) - Senior Research Associate (MRC Funded)
  • Phoebe Cheung, BSc (Imperial), MRes (Bristol) - PhD Student
  • Punyawee Dulyayangkul, BSc (Mahidol), PhD (CRI, Bangkok) - Research Associate (MRC Funded)
  • Winnie Lee, BSc (Herts), MRes (Imperial) - PhD Student
  • Beatriz Llamazares, BVSc (Leon), MSc (Copenhagen), MRCVS - PhD Student
  • Olly Mounsey, BSc, MRes (Bristol) - Technician (BBSRC Funded)
  • Naphat Satapoomin, BSc (Newcastle) - PhD Student
  • Jordan Sealey, BSc (Oxford Brooks), MSc (LSTM) - PhD Student
  • TBA - Research Associate (BBSRC Funded)

Project Management Team

  • Dr Ginny Gould - OH-STAR & OH-DART Project Manager (MRC/DoHSC Funded)
  • Dr Claire Spreadbury - AMR PhD Programme Manager (MRF Funded)
  • Pei-Si Hayes - AMR PhD Programme Deputy Manager (MRF Funded)
  • Carlos Ayala - FARMS-SAFE Project Manager (BBSRC/DoHSC Funded)
  • TBA - GW4 AMR Alliance Facilitator (GW4 Funded)

Collaborators

  • Prof Jim Spencer (CMM)
  • Dr Kate Heesom (Bristol Proteomics Facility)
  • Prof Kristen Reyher, MRCVS (Bristol Vet School)
  • Prof David Barrett, FRCVS (Bristol Vet School)
  • Dr Tristan Cogan (Bristol Vet School)
  • Prof Andrew Dowsey (Bristol Vet School)
  • Prof Alastair Hay, MRCGP (Bristol Medical School)
  • Prof Helen Lambert (Bristol Medical School)
  • Dr Ashley Hammond (Bristol Medical School)
  • Dr Massimo Antognozzi (Physics)
  • Prof Alasdair MacGowan FRCPath (Southmead Hospital)
  • Dr Martin Williams FRCPath (Bristol Royal Infirmary)
  • Dr Philip Williams FRCPath (Bristol Royal Infirmary)
  • Dr Maha Albur FRCPath (Southmead Hospital)
  • Dr Fergus Hamilton (Southmead Hospital)
  • Prof Skorn Mongkolsuk (Chulabhorn Research Institute)
  • Dr Jutamaad Satayavivad (Chulabhorn Research Institute)
  • Prof Visanu Thamlikitkul (Siriraj Hospital, Bangkok)
  • Dr Walasinee Sakcamduan (Mahidol University)
  • Dr Luechai Sringernyuang (Mahidol University)
  • Dr Aronrag Meeyai (University of Oxford)
  • Prof Henry Buller (University of Exeter)
  • Dr Emma Pitchforth (University of Exeter)
  • Dr Andrew Singer (NERC, Center for Ecology & Hydrology)
  • Prof Ed Feil (University of Bath)
  • Prof Luzbel de la Sota (University of La Plata)
  • Dr Nora Mestorino (University of La Pata)

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