
Dr Owen B. Spiller
Senior Lecturer
- Email:
- spillerb@cardiff.ac.uk
- Telephone:
- +44 29207 42394
- Location:
- UHW Main Building
- Available for postgraduate supervision
Dr. Owen “Brad” Spiller is a leading international authority on clinical Ureaplasma spp. and Mycoplasma hominis infections and has been the elected Secretary-General for the International Organisation of Mycoplasmology for the past 5 years. Currently his laboratory is the UK antimicrobial sensitivity reference laboratory for all Ureaplasma spp. and M. hominis positive clinical samples submitted to both Public Health England and Public Health Wales NHS services. In 2014, Brad was additionally appointed adjunct Associate Professor at the University of Western Australia, where he continues to serve as experimental infection advisor to the Large Animal Facility (School of Women’s and Infant’s Health) in Perth. Brad moved from the Department of Child Health to the Department of Medical Microbiology at Cardiff University in 2015, to join Professor Tim Walsh (Head) and Dr. Mark Toleman to form the All Wales Antimicrobial Resistance Research group (@AWARRe Twitter)
The Spiller Laboratory is a research team focussed on determining the underlying mechanisms of antimicrobial resistance (AMR) and pathogenicity in clinical infections, which have expanded from Mollicutes (cell-wall-less bacteria) to include Legionella pneumophila, Streptococcus agalactiae, and E. coli. The patient groups of interest are sepsis patients (both neonatal and adult) as well as diagnosis and treatment of non-specific urethritis/cervicitis in sexual health patients. These interests include validating new commercial diagnostic assays, developing new antimicrobial agents, developing new high-throughput AST screening platforms and examining suspected pathogenic/virulence genes (this is still the only laboratory that has successfully genetically altered Ureaplasma parvum to date (in collaboration with the Venter Institute). 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.
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 am in my third elected term as the Secretary-General of the International Organisation of Mycoplasmology (http://iom-online.org) and have just completed 2 elected terms as the mycoplasma antimicrobial resistance officer for the European Society of Clinical Microbiology and Infectious Diseases (https://www.escmid.org/research_projects/study_groups/mycoplasma_infections/executive_committee/).
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 associate professorship at the University of Western Australia's School of Women's and Infant's Health, Perth, Australia in 2014.
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.
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 Associate Professorship at the University of Western Australia
2020
- Spiller, O. B.et al. 2020. Mycoplasma genitalium prevalence in Welsh sexual health patients: low antimicrobial resistance markers and no association of symptoms to bacterial load. Microbial Pathogenesis 139, article number: 103872. (10.1016/j.micpath.2019.103872)
2019
- Hütten, M. C.et al. 2019. Detrimental effects of an inhaled phosphodiesterase-4 inhibitor on lung inflammation in ventilated preterm lambs exposed to chorioamnionitis are dose dependent. Journal of Aerosol Medicine and Pulmonary Drug Delivery, pp. -. (10.1089/jamp.2019.1528)
- van Gorp, C.et al. 2019. Protection of the ovine fetal gut against ureaplasma-induced chorioamnionitis: a potential role for plant sterols. Nutrients 11(5), pp. -., article number: 968. (10.3390/nu11050968)
2017
- Yang, Q.et al. 2017. Balancing mcr-1 expression and bacterial survival is a delicate equilibrium between essential cellular defence mechanisms. Nature Communications 8, article number: 2054 (2017). (10.1038/s41467-017-02149-0)
- Gussenhoven, R.et al. 2017. The paradoxical effects of chronic intra-amniotic Ureaplasma exposure on ovine fetal brain development. Developmental Neuroscience 39(6), pp. 472-486. (10.1159/000479021)
- Willems, M. G. M.et al. 2017. Pulmonary vascular changes in extremely preterm sheep after intra-amniotic exposure to Ureaplasma parvum and lipopolysaccharide. PLoS ONE 12(6), article number: e0180114. (10.1371/journal.pone.0180114)
- Spiller, O. B. 2017. Emerging pathogenic respiratory mycoplasma hominis infections in lung transplant patients: time to reassesses it's role as a pathogen?. EBioMedicine 19, pp. 8-9. (10.1016/j.ebiom.2017.05.002)
- Hillitt, K. L.et al. 2017. Antimicrobial activity of Manuka honey against antibiotic resistant strains of the cell wall free bacteria ureaplasma parvum and Ureaplasma urealyticum. Letters In Applied Microbiology 64(3), pp. 198-202. (10.1111/lam.12707)
- Beeton, M. and Spiller, O. B. 2017. Antibiotic resistance among Ureaplasma spp isolates: cause for concern?. Journal of Antimicrobial Chemotherapy 72(2), pp. 330-337. (10.1093/jac/dkw425)
- Kemp, M.et al. 2017. Fetal Ureaplasma parvum bacteraemia as a function of gestation-dependent complement insufficiency: evidence from a sheep model of pregnancy. American Journal of Reproductive Immunology 77(1), article number: e12599. (10.1111/aji.12599)
- Stock, S. J.et al. 2017. Intrauterine Candida albicans infection causes systemic fetal candidiasis with progressive cardiac dysfunction in a sheep model of early pregnancy. Reproductive Sciences 24(1), pp. 77-84. (10.1177/1933719116649697)
2016
- Jironkin, A.et al. 2016. Genomic determination of minimum multi-locus sequence typing schemas to represent the genomic phylogeny of Mycoplasma hominis.. BMC Genomics 17 (10.1186/s12864-016-3284-z)
- Aboklaish, A.et al. 2016. Differential recognition of the Multiple Banded Antigen isoforms across Ureaplasma parvum and Ureaplasma urealyticum species by monoclonal antibodies. Journal of Microbiological Methods 127, pp. 13-19. (10.1016/j.mimet.2016.05.015)
- Beeton, M.et al. 2016. Isolation of separate Ureaplasma species from endotracheal secretions of twin patients. Pediatrics 138(2) (10.1542/peds.2016-0565)
- Brown, R.et al. 2016. Mycoplasma pneumoniae epidemiology in England and Wales: a national perspective. Frontiers in Microbiology 7, article number: 157. (10.3389/fmicb.2016.00157)
- Kemp, M. W.et al. 2016. Outside-in? Acute fetal systemic inflammation in very preterm chronically catheterized sheep fetuses is not driven by cells in the fetal blood. American Journal of Obstetrics and Gynecology 214(2), pp. 281.e1-281.e10. (10.1016/j.ajog.2015.09.076)
- Beeton, M. L.et al. 2016. Antibiotic resistance among clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013. Antimicrobial Agents and Chemotherapy 60(1), pp. 52-56. (10.1128/AAC.00889-15)
2015
- Nesargikar, P.et al. 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., 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)
- Brown, R.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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.et al. 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)
New publication updates! Nov 2019
Free access to our latest analysis of 1000 Welsh sexual health patients in rural Wales: https://authors.elsevier.com/a/1a7qV38ed-Ja%7Eu until 16 Jan 2020. Looking at the prevalence of the emerging Sexual Health Superbug Mycoplasma genitalium. New important evidence: bacterial load is NOT related to symptoms and age group for peak incidence differs between genders.
Sexual Health Patient Research
There are currently 3 separate KESS2-funded active research projects:
- In collaboration with industrial partner Health First Consulting, to evaluate the specificity, sensitivity and AMR accuracy of the CPM SAS (Italy) MYCO WELL D-ONE assay on 1000 Welsh patients attending walk-in Sexual Health NHS clinics in Rhondda Cynon Taf. Collection of these samples has concluded as of October 2018. A follow-on IRAS ethics has now been obtained to correlate specific sexual health diagnoses to presence (as well as bacterial load thresholds) for Ureaplasma parvum, Ureaplasma urealyticum, Mycoplasma hominis and Mycoplasma genitalium infection. These studies were also able to incorporate development of a new parC-mutation diagnostic assay from SpeeDx, which will shortly be published. (MPhil student Daniel Morris, Medical student Christopher Rees)
- In collaboration with industrial partner, Cwm Taf University Health Trust, to evaluate the specificity, sensitivity and AMR accuracy of the CPM SAS (Italy) UROGEN WELL D-ONE assay and the BioMerieiux (France) prototype for Mycoplasma IST3 assay on 500 symptomatic sexual health patients attending walk-in sexual health clinics at Keir Hardie Health park and Dewi Sant Hospital. Similar to the previous study, however this chromogenic culture diagnostic assay extends to Neisseria spp., E. coli, Group B Streptococcus, Candida, Trichomonas vaginalis, Gardnerella vaginalis, Staphylococcus and Enterococcus spp. Multifactorial and odds ratio associations for each microbe will be determined for urethritis, cervicitis, pelvic inflammatory disease and other relevant sexual health maladies. This study will continue recruiting until September 2019. (MPhil student Andrew Barratt/technical assistance Ian Boostrom)
- In collaboration with industrial partners Public Health Wales and Cwm Taf University Health Trust, an interventional clinical trial (THE ANTIBIOTIC GUARDIAN study) will determine the benefits of rapid targeted therapeutic intervention on the rate of clinical symptom resolution for patients and number of clinical visits to sexual health clinics. This project is also designed to reduce the amount of incorrect antimicrobial prescription and determine effective working antibiotic guardian guidelines without diminishing patient care. (PhD student Martin Sharratt, Nurse Rebecca Davis)
Legionella pneumophila research
Legionella pneumophila is a remarkably fastidious bacteria and it’s requirement for addition of activated charcoal to agar-based culture has long interfered with the capacity to determine antimicrobial susceptibility testing. Activated charcoal not only makes it difficult to visualise the growth of bacteria on the plate (requiring evaluation of the plate surface with removal of the lid putting the investigator at risk of aerosol exposure to a potent respiratory pathogen), but it also absorbs the antimicrobials to varying extents making it impossible to define an accurate AST or determine AMR. While microbroth dilution methods are available, they are extremely tedious and require evaluation of turbidity on multiple 96-well plates. We have created a translucent solid culture medium (LASARUS – patent pending), that we have combined with automated multi-pin-inoculation and have currently determined the MIC for 8 antimicrobials on all archived clinical isolates submitted to Public Health England and Wales since 2003 (approximately 2000 isolates) as well as an additional 1000 environmental isolates from PHE Porton Downs. An important advance as the previous record for AST determination for Legionella pneumophila was 122 isolates! We are now adapting our high throughput platform to determine biocide efficacy and to evaluate a series of new antimicrobials/decontaminants. (PhD student Edward Portal)
Streptococcus agalactiae research
We have finished comparing whole genome sequences for 195 blood isolated strains collected between 2014-2015 (in collaboration with Public Health England and supported by the Fiona Elizabeth Agnew Trust) relative to AST determination to correlate all the available antimicrobial resistance and virulence genes to patient outcome. The results of these studies will be presented at the FEMS meeting in Glasgow July 2019. The research programme is now expanding to compare UK isolate genomes to all invasive blood and CSF isolates from Sao Paolo Brazil (collaboration with Diego Andrey – Switzerland and Ana Gales – Brazil) and strains collected during routine antenatal screening in Perth Australia. (PhD student Uzma Basit Khan).
Molecular manipulation of Ureaplasma parvum
Although commonly dismissed as a commensal, there is no escaping the dominant association of Ureaplasma infection and preterm birth – or at a minimum the key role of Ureaplasma respiratory infection of preterm infants and the development of chronic lung disease. Routine clinical evaluation of preterm neonates at the Children’s Hospital at University Hospital of Wales has determined that successful transfer from invasive mechanical ventilator assisted breathing to non-invasive continuous positive airway pressure – assisted breathing requires successful treatment of underlying Ureaplasma spp. infections. This is particularly difficult as all Ureaplasma spp. are inherently resistant to all antimicrobials except for tetracyclines, fluoroquinolones and macrolides. The first two of which cannot be used in children due to adverse effects on teeth/bones and tendons/ligaments respectively. Not all strains are pathogenic and there is a void in the information regarding the mechanisms of pathogenicity or identification of virulence genes for this organism as they are one of the smallest (200-500 nm) and most difficult to culture. Following on from our previous unique success as the only laboratory to successfully achieve random insertion mutagenesis inactivation of genes, we have now delivered luciferase genes that allow visualisation of these organisms following engulfment my leukocytes and in vivo tracking of infection in experimental models.