Dr Brad Spiller

Reader

: SpillerB@cardiff.ac.uk
: +44 29207 42394
: Main Hospital Building, Floor 6th, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN

: Available for postgraduate supervision

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 Microbiolist 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.

2015

Brown, R., Spiller, O. B. and Chalker, V. J. 2015. Molecular typing of mycoplasma pneumoniae: where do we stand?. Future Microbiology 10(11), pp. 1793-1795. (10.2217/fmb.15.96)
Nesargikar, P., Pino-Chavez, G., Spiller, O. B., Fraser, D. J., Jenkins, R. H. and Chavez, R. 2015. Single dose sCR1 attenuates renal ischemia reperfusion injury in rats despite early reconstitution of the complement system [Abstract]. Transplant International 28(S4), pp. 62-62. (10.1111/tri.12700)
Brown, R., Holden, M. T. G., Spiller, O. B., Chalker, V. J. and Ledeboer, N. A. 2015. Development of a multilocus sequence typing scheme for molecular typing of mycoplasma pneumoniae. Journal of Clinical Microbiology 53(10), pp. 3195-3203. (10.1128/JCM.01301-15)
Furfaro, L. L., Spiller, O. B., Keelan, J. A. and Payne, M. S. 2015. In vitro activity of solithromycin and its metabolites, CEM-214 and N-acetyl-CEM-101, against 100 clinical Ureaplasma spp. isolates compared with azithromycin. International Journal of Antimicrobial Agents 46(3), pp. 319-324. (10.1016/j.ijantimicag.2015.04.015)
Ahmed, S. et al. 2015. Comparison of complement activity in adult and preterm sheep serum. American Journal of Reproductive Immunology 73(3), pp. 232-241. (10.1111/aji.12299)

2014

Aboklaish, A., Dordet-Frisoni, E., Citti, C., Toleman, M. A., Glass, J. I. and Spiller, O. B. 2014. Random insertion and gene disruption via transposon mutagenesis of Ureaplasma parvum using a mini-transposon plasmid. International Journal of Medical Microbiology 304(8), pp. 1218-1225. (10.1016/j.ijmm.2014.09.003)
Kemp, M. W. et al. 2014. Maternal intravenous administration of azithromycin results in significant fetal uptake in a sheep model of second trimester pregnancy. Antimicrobial Agents and Chemotherapy 58(11), pp. 6581-6591. (10.1128/AAC.03721-14)
Kemp, M. W. et al. 2014. Repeated maternal intramuscular or intraamniotic erythromycin incompletely resolves intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. American Journal of Obstetrics and Gynecology 211(2), pp. 134.e1-134.e9. (10.1016/j.ajog.2014.02.025)
Lowe, J., Watkins, W., Edwards, M., Spiller, O., Jacqz-Aigrain, E., Kotecha, S. and Kotecha, S. 2014. Association between pulmonary Ureaplasma colonization and bronchopulmonary dysplasia in preterm infants: updated systematic review and meta-analysis. The Pediatric Infectious Disease Journal 33(7), pp. 697-702. (10.1097/INF.0000000000000239)
Miura, Y. et al. 2014. Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection. Antimicrobial Agents and Chemotherapy 58(9), pp. 5413-5420. (10.1128/AAC.03187-14)
Van Den Berg, C., Tambourgi, D. V., Clark, H. W., Hoong, S. J., Spiller, O. and McGreal, E. 2014. Mechanism of neutrophil dysfunction: neutrophil serine proteases cleave and inactivate the C5a receptor. The Journal of Immunology 192(4), pp. 1787-1795. (10.4049/jimmunol.1301920)
Brown, R., Chalker, V. J. and Spiller, O. B. 2014. Mycoplasma hominis variable adherence-associated antigen: A major adhesin and highly variable surface membrane protein. Advances in Microbiology 4(11), pp. 736-746. (10.4236/aim.2014.411080)

2013

Payne, M. S., Tabone, T., Kemp, M. W., Keelan, J. A., Spiller, O. B., Newnham, J. P. and Carroll, K. C. 2013. High-resolution melt PCR analysis for genotyping of Ureaplasma parvum isolates directly from clinical samples. Journal of Clinical Microbiology 52(2), pp. 599-606. (10.1128/JCM.03036-13)
Triantafilou, M., De Glanville, B., Aboklaish, A. F., Spiller, O. B., Kotecha, S. and Triantafilou, K. 2013. Synergic activation of Toll-Like Receptor (TLR) 2/6 and 9 in response to ureaplasma parvum & urealyticum in human amniotic epithelial cells. PLoS ONE 8(4), article number: e61199. (10.1371/journal.pone.0061199)

2012

Beeton, M. L., Daha, M. R., El-Shanawany, T., Jolles, S., Kotecha, S. and Spiller, O. B. 2012. Serum killing of 'ureaplasma parvum' shows serovar-determined susceptibility for normal individuals and common variable immuno-deficiency patients. Immunobiology 217(2), pp. 187-194. (10.1016/j.imbio.2011.07.009)
McGreal, E. P., Hearne, K. and Spiller, O. B. 2012. Off to a slow start: under-development of the complement system in term newborns is more substantial following premature birth. Immunobiology 217(2), pp. 176-186. (10.1016/j.imbio.2011.07.027)

2011

Pinkert, S., Klingel, K., Lindig, V., Dorner, A., Zeichhardt, H., Spiller, O. B. and Fechner, H. 2011. Virus-host coevolution in a persistently coxsackievirus B3-infected cardiomyocyte cell line. Journal of Virology 85(24), pp. 13409-13419. (10.1128/JVI.00621-11)
Beeton, M. L. et al. 2011. Role of pulmonary infection in the development of chronic lung disease of prematurity. European Respiratory Journal 37(6), pp. 1424-1430. (10.1183/09031936.00037810)

2010

McGreal, E. P. et al. 2010. Inactivation of IL-6 and soluble IL-6 receptor by neutrophil derived serine proteases in cystic fibrosis. Biochimica et Biophysica Acta - Molecular Basis of Disease 1802(7-8), pp. 649-658. (10.1016/j.bbadis.2010.04.005)
Davies, P. L., Spiller, O. B., Beeton, M. L., Maxwell, N. C., Remold-O'Donnell, E. and Kotecha, S. 2010. Relationship of proteinases and proteinase inhibitors with microbial presence in chronic lung disease of prematurity. Thorax 65(3), pp. 246-251. (10.1136/thx.2009.116061)

2009

Beeton, M. L., Chalker, V. J., Maxwell, N. C., Kotecha, S. and Spiller, O. B. 2009. Concurrent titration and determination of antibiotic resistance in 'ureaplasma' species with identification of novel point mutations in genes associated with resistance. Antimicrobial Agents and Chemotherapy 53(5), pp. 2020-2027. (10.1128/AAC.01349-08)
Wall, S. R., Wat, D., Spiller, O. B., Gelder, C. M., Kotecha, S. and Doull, I. J. M. 2009. The viral aetiology of croup and recurrent croup. Archives of Disease in Childhood 94(5), pp. 359-360. (10.1136/adc.2008.142984)
Okroj, M. et al. 2009. Characterization of the complement inhibitory function of rhesus rhadinovirus complement control protein (RCP). Journal of Biological Chemistry 284(1), pp. 505-514. (10.1074/jbc.M806669200)
Beeton, M. L., Chalker, V. J., Kotecha, S. and Spiller, O. B. 2009. Comparison of full gyrA, gyrB, parC and parE gene sequences between all Ureaplasma parvum and Ureaplasma urealyticum serovars to separate true fluoroquinolone antibiotic resistance mutations from non-resistance polymorphism. Journal of Antimicrobial Chemotherapy 64(3), pp. 529-538. (10.1093/jac/dkp218)
Pinkert, S. et al. 2009. Prevention of cardiac dysfunction in acute coxsackievirus B3 cardiomyopathy by inducible expression of a soluble coxsackievirus-adenovirus receptor. Circulation 120(23), pp. 2358-2366. (10.1161/CIRCULATIONAHA.108.845339)

2008

Griesche, N. et al. 2008. Growth characteristics of human adenoviruses on porcine cell lines. Virology 373(2), pp. 400-410. (10.1016/j.virol.2007.12.015)
Mark, L., Proctor, D. G., Blackbourn, D. J., Blom, A. M. and Spiller, O. B. 2008. Separation of decay-accelerating and cofactor functional activities of Kaposi's sarcoma-associated herpesvirus complement control protein using monoclonal antibodies. Immunology 123(2), pp. 228-238. (10.1111/j.1365-2567.2007.02692.x)
Davies, P. L., Maxwell, N. C., Kotecha, S. and Spiller, O. B. 2008. Monoclonal anti-neutrophil elastase antibody characterisation: ability to block function, detect free versus serpin-complexed enzyme and stain intracellular granules. Journal of Immunological Methods 336(2), pp. 175-182. (10.1016/j.jim.2008.04.010)

2006

Spiller, O. B., Mark, L., Blue, C. E., Proctor, D. G., Aitken, J. A., Blom, A. M. and Blackbourn, D. J. 2006. Dissecting the regions of virion-associated Kaposi's sarcoma-associated herpesvirus complement control protein required for complement regulation and cell binding. Journal of Virology 80(8), pp. 4068-4078. (10.1128/JVI.80.8.4068-4078.2006)

2005

Spiller, O. B., Goodfellow, I. G., Evans, D. and Blom, A. M. 2005. Inhibition of coxsackie B virus infection by soluble forms of its receptors: binding affinities, altered particle formation, and competition with cellular receptors. Journal of Virology 79(18), pp. 12016-12024. (10.1128/JVI.79.18.12016-12024.2005)

2003

Spiller, O. B., Blackbourn, D. J., Mark, L., Proctor, D. G. and Blom, A. M. 2003. Functional activity of the complement regulator encoded by Kaposi's sarcoma-associated herpesvirus. Journal of Biological Chemistry 278(11), pp. 9283-9289. (10.1074/jbc.M211579200)
Spiller, O. B., Robinson, M., O'Donnell, E., Milligan, S., Morgan, B. P., Davison, A. J. and Blackbourn, D. J. 2003. Complement regulation by Kaposi's sarcoma-associated herpesvirus ORF4 protein. Journal of Virology 77(1), pp. 592-599. (10.1128/JVI.77.1.592-599.2003)

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).

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

Current supervision

Martin Sharratt

Research student

Ian Boostrom

Lab Manager, Medical Microbiology Research

Jawaria Aziz

Research student

Jordan Mathias

Research Assistant

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 infections” Successfully 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 Adults” Successfully 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.

Research themes

Specialisms

Antimicrobial resistance

Dr Brad Spiller

2023

2022

2021

2020

2019

2017

2016

2015

2014

2013

2012

2011

2010

2009

2008

2006

2005

2003