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Brad Spiller

Dr Brad Spiller

Reader

School of Medicine

Email
SpillerB@cardiff.ac.uk
Telephone
+44 29207 42394
Campuses
Main Hospital Building, Floor 6th, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
Users
Available for postgraduate supervision

Overview

I am currently the Head of Medical Microbiology for the Division of Infection & Immunity, which spans the 6th Floor of the University Hospital of Wales. I also have Honorary Consulting Microbiologist positions with both the UK Health Security Agency and the Cwm Taf Morgannwg NHS Trust and an Adjunct Associate Professorship with the University of Western Australia since 2014.  I am a leading international authority on clinical Ureaplasma spp. and Mycoplasma hominis infections and held the elected position of Secretary-General for the International Organisation of Mycoplasmology from 2014-2021.  My laboratory currently serves as the UK Antimicrobial Sensitivity Testing Reference Laboratory for all Ureaplasma spp. and M. hominis positive clinical samples submitted to both UKHSA (formerly Public Health England) and Public Health Wales NHS services.  Updates for Medical Microbiology are posted for the All Wales Antimicrobial Resistance Research group (@AWARRe Twitter).

Currently, the Spiller Laboratory is leading collaborative investigations (funded by Ineos Oxford Institute) of all Gram-positive bacterial infections in neonatal sepsis originating from Low-to-Middle income countries (LMIC) as part of BARNARDS phase II (Burden of Antibiotic Resistance in Neonates from Developing Societies). Antimicrobial susceptibility, whole genome sequence analysis, virulence and transfer of antimicrobial resistance genes from one bacteria to another are characterised for blood stream isolated Gram-positive bacteria. Participating collaborative hospital sites are currently located inPakistan, Nigeria, Bangladesh, Rwanda, Ethiopia, South Africa (BARNARDs phase 1), Niger (Combacte-Care), Egypt, Sierra Leone, Mozambique, Burundi (hopefully as expanding as part of BARNARDs phase 2) and Uganda (PROGRESS).

Other studies running in parallel investigate the underlying mechanisms of antimicrobial resistance (AMR) and pathogenicity in clinical infections that include Mollicutes (cell-wall-less bacteria) Gram-negative bacteria (including Legionella pneumophila, Klebsiella pneumoniae and E. coli) and UK invasive Gram-positive bacterial infections in adults (including Streptococcus agalactiae, Streptococcus sinensis, Streptococcus viridans and Streptococcus cristatus).  The laboratory also includes the Cardiff University Bacterial Whole Genome Sequencing facility, that runs collaborative projects with Welsh Gene Park, Public Health Wales (ARGENT project) and the Ineos Oxford Institute.  The patient groups of interest are sepsis patients (both neonatal and adult; and located in the UK, Cuba, Uganda and Ghana), UK Legionellosis outbreaks, as well as diagnosis and treatment of non-specific urethritis/cervicitis in Welsh sexual health patients.  Research foci include validating new commercial diagnostic assays, developing new antimicrobial agents, developing new high-throughput AST screening platforms and examining suspected pathogenic/virulence genes. The Spiller Laboratory is particularly proud to still be the only laboratory that has successfully genetically altered Ureaplasma parvum to date to allow ex vivo imaging for experimental ascending infection studies (in collaboration with the University of Edinburgh).  Due to expanding collaborations within AWARRe the Spiller Laboratory also takes an active role in collaborative research on emerging AMR-mediating genes (such as mcr-1, NDM-5, etc) in vitro and in vivo.

As of 2021, the Spiller Laboratory has also set up active bilateral research sites to investigate antimicrobial resistance prevalence in both Cape Coast Teaching Hospital in Ghana and the Department of Obstetrics and Gynaecology Makerere University and Kawempe National Referral Hospital, Uganda.

Publication

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Articles

Research

Investigation of neonatal sepsis in Low-to-Middle income countries (LMIC)

The Spiller laboratory is the hub for characterising Gram-positive pathogens that are isolated from the blood stream of neonates in the first 30 days of life. Antimicrobial susceptibility, whole genome sequence analysis, virulence and transfer of antimicrobial resistance genes from one bacteria to another are characterised for isolates from Pakistan, Nigeria, Bangladesh, Rwanda, Ethiopia, South Africa (BARNARDs phase 1), Niger (Combacte-Care), Egypt, Sierra Leone, Mozambique, Burundi (hopefully as expanding as part of BARNARDs phase 2) and Uganda (PROGRESS). Active collaborations for these studies include University of Oxford, Médecins Sans Frontières and St. George's, University of London. These studies currently extend to improving microbiological diagnostic tools better suited to low resource settings to enable faster and more informed treatment of invasive Gram-positive infections in LMICs.

Group B Strep (Streptococcus agalactiae) research

The laboratory has a particular interest in characterising the mobility of Integral Conjugative Elements carrying accumulations of antibiotic resistance genes in GBS. Beyond work examining neonatal sepsis in LMICs, the laboratory also has active collaborations with the UK Health Security Agency, Sanger Sequencing Institute Cambridge and St. George’s University London to characterise increases in antimicrobial resistance in invasive GBS in all age groups.

Revolutionary New Legionella media patented.

In collaboration with the UK Health Security Agency, the Spiller laboratory has patented a new solid Legionella medium (Legionella Antimicrobial Susceptibility And Resistance Universal Screening medium: LASARUS) that replaces activated charcoal-containing medium. The new medium is transparent and does not absorb antimicrobials like all traditional solid agar. We are currently determining the susceptibility of over 2000 archived clinical and environmental Legionella spp. isolates using LASARUS and a high-throughput inoculation method. The Spiller lab is also currently coordinating the international standardisation of antimicrobial susceptibility testing for Legionella pneumonia and other clinical Legionella species in Legionella reference laboratories across Europe and at the CDC. This latter project is currently being supported through funding by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID).

Sexual Health Patient Research

The Spiller laboratory has been the UK reference laboratory for antimicrobial susceptibility testing of Ureaplasmas and Mycoplasmas for the UK Health Security Agency for the past decade. This arises from an internationally recognised expertise for these sexually transmitted infections. There have been 3 previously funded studentships that have now come to a conclusion examining the epidemiology, antimicrobial resistance prevalence and pathogenicity in Welsh Sexual Health patients in collaboration with our clinical lead Dr. Lucy Jones. These studies include: (1) the MYCO WELL D-ONE study (2016-2017; IRAS ) examining 1000 Welsh patients attending walk-in Sexual Health NHS clinics in Rhondda Cynon Taf for infection by Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium. (2) The UROGEN study (2017-2018; IRAS ), which included the first validation of the Mycoplasma IST3 assay ( BioMerieiux, France) on 500 symptomatic sexual health patients attending walk-in sexual health clinics at Keir Hardie Health park and St David's Hospital. This project expanded to include chromogenic culture diagnostic assays for Neisseria spp., E. coli, Group B Streptococcus, Candida, Trichomonas vaginalis, Gardnerella vaginalis, Staphylococcus and Enterococcus spp. and (3) The Antibiotic Guardian Study (2019-2022), in collaboration with Public Health Wales and Cwm Taf University Health Trust, that examined the feasibility of directing rapid targeted therapeutic intervention using commercial SpeeDx assays for detecting resistant infections of Mycoplasma and Neisseria gonorrhoea.

Currently our laboratory is collaborating with Public Health Wales to reevaluate culture based antimicrobial susceptibility testing for Neisseria gonorrhoea as well (Master’s student Leanne Davies).

 

Biography

Originally a Canadian Microbiologist from Vancouver, I initially came to the U.K. to examine innate immune evasion of microbes. From 2000 to 2005 I established an independed research group through the Wellcome Trust Career Development Fellowship Program, before joining the Department of Child Health at University Hosptial of Wales in 2005 to develop a new research theme examining antimicrobial resistance in bacterial infections of premature neonates.  This led to my establishing the leading U.K. reference laboratory for investigations of Mycoplasma and Ureaplasma infections. These cell wall-less bacteria are inherently resistant to most antimicrobials and are the leading cause of preterm birth and are emerging as respiratory pathogens.  I recently completed my third elected term as the Secretary-General of the International Organisation of Mycoplasmology.

In 2012, I began a Royal Society funded collaboration with the University of Western Australia to investigate intrauterine microbial pathology and develop new antibiotics that were safe and effective for use in pregnant women.  These collaborations resulted in my being awarded an adjunct Assistant Professorship at the University of Western Australia's School of Women's and Infant's Health, Perth, Australia in 2014. The success of the Cardiff-Australia collaborations led to a promotion to Associate Professor in 2021.

Also in 2015, I joined the All Wales Antimicrobial Resistance Research unit, headed by Prof. Timothy Walsh, and have been expanding my research of antimicrobial resistance to other bacteria.  As a result in 2017, I have new research projects characterising Group B Streptococcus strains isolated from U.K. sepsis patients and characterisation of Legionella pnuemophilia isolates from U.K. outbreaks of Legionnaires' disease, also known as legionellosis.  

In 2020, I was appointed as Head of Medical Microbiology where I continue to support and expand our team of researchers including early career researchers and academic clinicians.  Currently I lead the characterisation of Gram-positive blood stream isolates in neonates across Africa and South East Asia in collaboration with the Ineos Oxford Institute (24 sites across 8 countries: BARNARDS phase 2), as well as leading the international standardisation to unify the Antimicrobial Resistance Testing for Legionella across Europe. 

Education and qualifications:

1995: PhD (Pathology), University of British Columbia, Vancouver, B.C. Canada

Honours and awards

  • 2000 Wellcome Trust Research Career Development Fellowship
  • 2015 Awarded Honorary Adjunct Assistant Professorship at the University of Western Australia
  • 2020 Awarded the Derrick Edward Award for contribution to the field of Mycoplasmology by the International Organisation of Mycoplasmology
  • 2020 Awarded Honorary contract for Consulting Microbiologist with Public Health England
  • 2021 Promoted to Honorary Adjunct Associate Professorship at the Universtiy of Western Australia

Supervisions

Current supervision

Martin Sharratt

Martin Sharratt

Research student

Ian Boostrom

Ian Boostrom

Lab Manager, Medical Microbiology Research

Jawaria Aziz

Jawaria Aziz

Research student

Jordan Mathias

Jordan Mathias

Research Assistant

Leanne Davies

Leanne Davies

Research student

Past projects

Apr. 2023-Apr. 2024   Leanne Davies  (primary supervisor for M.Phil in Med Micro)  Evaluation of media for the susceptibility testing of N. gonorrhoeae.

Jan. 2023-Jan. 2027   Jawaria Aziz (primary supervisor for Ph.D. in Med Micro)  The burden of Coagulase-negative Staphylococci antimicrobial resistance in neonatal sepsis in the LMIC

Jan. 2023-Jan. 2027   Jordan Mathias (primary supervisor for Ph.D. in Med Micro)  The burden of Staphylococcus aureus antimicrobial resistance in neonatal sepsis in the LMIC

Jul. 2021-Jul. 2025     Ian Boostrom (primary supervisor for Ph.D. in Med Micro)  Improving detection of Legionella species from environmental and clinical sources)

Sep. 2019-Sep. 2023   Martin Sharratt (primary supervisor for Ph.D. in Med Micro)  The Antibiotic Guardian Study (targeted therapeutics based on rapid diagnostics)

Sep. 2018-Sep. 2021   Mei Li (replacement supervisor for Ph.D. in Med Micro)  “Assessment of global impact of mcr-1/mcr-3 mediated colistin resistance” Successfully defended

Jan. 2018-Jan. 2021   Katy Thomson (replacement supervisor for Ph.D. in Med Micro)  Assessment of antibiotic resistance in pathogens causing neonatal sepsis, associated mortality and recommended treatment options in low- and middle- income countries” Successfully defended 16/12/2022

Sep. 2017-Sep. 2021   Dr. Edward Portal  (primary supervisor for Ph.D. in Med Micro)  Phylogenetics, sequence-type characterisation and persistence of Legionella pneumophila in patients and the environment” Successfully defended 23/02/2022

Sep. 2017-Sep. 2021   Dr. Uzma Basit Khan  (primary supervisor for Ph.D. in Med Micro)  Detailed genomic and antimicrobial resistance comparison of UK Streptococcus agalactiae isolates from adults to those of diverse global origins” Successfully defended 22/02/2021

Sep. 2014-Sep. 2018   Dr. Qui Yang  (co-supervisor for Ph.D. in Med Micro)  Multifaceted aspects of MCR-mediated colistin resistance: Fitness, virulence, environmental reservoirs and genomic insights” Successfully defended 02/10/201513/08/2018

Oct. 2017-Sep. 2019   Mr. Daniel Morris  (primary supervisor for MPhil. in Med Micro)  MYCO WELL D-ONE: Can a new rapid diagnostic test for Ureaplasma and Mycoplasma detect infectionsSuccessfully defended 19/07/2019

Sep. 2012-Sep. 2015   Dr. Shatha Ahmed  (primary supervisor for Ph.D. in Child Health)  Antigenic Ureaplasma variation and adaptation to in vivo and in vitro immune pressure” Successfully defended 02/10/2015

Oct. 2012-Oct. 2015   Miss. Rebecca Brown  (primary supervisor for Ph.D. in Child Health)  Determining Mycoplasma susceptibility to and evasion from the innate immune system” Successfully defended 16/06/2016.

Jan. 2011-Jan. 2015   Mrs. Amina Bshina  (primary supervisor for Ph.D. in Child Health)  Intracellular and cell-surface Neutrophil proteinase levels and distribution: changes following extravasation and microbial infection” Successfully defended 05/02/2015

Jan. 2010-Jan. 2014   Mr. Ali Aboklaish (primary supervisor for Ph.D. in Child Health)  “Determining the Immunodominant antigens from Ureaplasma parvum and their stability under immunological pressure Successfully defended 01/12/2014.

Oct. 2009-Oct. 2010   Dr. Salima Abdulla (primary supervisor for M.D. in Child Health)  “Developmental Innate Immunodeficiency: Comparison of Term Neonatal Neutrophil Proteinase and Complement component levels relative to AdultsSuccessfully defended 07/12/2012

Oct. 2006-Oct. 2009   Mr. Michael Beeton (primary supervisor for Ph.D. in Child Health)  Mechanism of Macrolide (antibiotic) resistance of Ureaplasma isolated from Newborn Preterm Infants.” Successfully defended 31/03/2010.

Mar. 2006-Mar. 2007 Dr. Phil Davies (co-supervisor for M.D. in Child Health)  “Presence and pharmaceutical administration of alpha-1-anti-trypsin in paediatric lung disease and cystic fibrosis.”  Successfully defended 25 June 2008.