Role of Ureaplasma spp.in human infection
My primary research interest focuses on the pathogens Ureaplasma parvum and Ureaplasma urealyticum.Ureaplasma spp. are the most commonly isolated organism from the chorioamnion and amniotic fluid among patients presenting with preterm labour and have been associated with numerous chronic infections such as bronchopulmonary dysplasia (BPD), non-gonococcal urethritis (NGU) and infectious arthritis.
My focused research interests include:
Monitoring the prevalence and mechanisms of antibiotic resistance among UK Ureaplasma isolates
- Treatment of Ureaplasma infections are complicated due to a lack of effective antibiotics as a consequence of the unique physiology of these organisms. Treatment options are further restricted among preterm neonates due to the contraindication of some antibiotics as a result of associated toxicities in this patient group. A final confounding factor in treatment is the presence of antibiotic resistant strains. In collaboration with Dr Brad Spiller (Cardiff University) and Dr Vicki Chalker (Public Health England) we have successfully monitored the prevalence of acquired antibiotic resistance among UK populations over a number of years. These data have been used to guide clinical practice as well as compare UK figures with those on an international scale.
- There is a strong association between the presence of bacterial biofilms and development of chronic infections. Although these bacterial communities and their impact on disease are well characterised for many pathogens, very little is known with respect to Ureaplasma spp. Using a variety of in vitro static and flow models, in addition to in vivo models, in collaboration with the University of Western Australia, my research group has been able to further understand the how Ureaplasma spp., which are self-toxic over time, are able to exist in such communities.
The role in which Ureaplasma spp. play in the development of NGU has been controversial, but recent findings have indicated a number of risk factors for symptomatic outcome. The Beeton research group aim to characterise the host immune response among males presenting with NGU as a result of Ureaplasma colonisation.
Confocal scanning laser microscopy image of 72 hour U. parvum biofilms.
Adherent cells were then stained with (left) Syto9 or (right) Hoechst 33342 after a total of 72 hours.
Invertebrate models of infection
As part of my post-doctoral work I became interested in the use of invertebrates as a model for infection. Compared with mammalian models this system is cost effective, does not require specialised housing facilities and benefits from reduced ethical implications. These factors make the invertebrate model a feasible intermediate between in vitro studies and larger scale in vivo mammalian work. I have successfully used these models to examine bacterial virulence factors as well to test novel anti-invectives therapies.
The Galleria mellonella infection model provides a reliable and inexpensive means to examine the virulence of pathogens as well as examining the efficacy of novel antimicrobial compounds in vivo. G. mellonella on the left have received sterile saline, whereas those on the right have received a lethal dose of P. aeruginosa.
Beeton ML and Spiller OB. Antibiotic resistance among Ureaplasma spp isolates; cause for concern? J Antimicrob Chemother. 2016. In Press
Kemp MW, Ahmed S, Beeton ML, Payne MS, Saito M, Mirua Y, Usuda H, Kallapur SG, Kramer BW, Stock SJ, Jobe AH, Newnham JP, Spiller OB.Fetal Ureaplasma parvum bacteraemia as a function of gestation-dependent complement insufficiency: evidence from a sheep model of pregnancy. 2016. In Press
Hillitt K, Jenkins RE, Spiller OB and Beeton ML. Antimicrobial activity of Manuka honey against antibiotic resistant strains of the cell wall free bacteria Ureaplasma parvum and Ureaplasma urealyticum. Lett Appl Microbiol. 2016 Dec 19. doi: 10.1111/lam.12707
Beeton ML, Maxwell NC, Chalker VJ, Brown RJ, Aboklaish AF, Spiller OB; ESCMID Study Group for Mycoplasma Infections. Isolation of Separate Ureaplasma Species From Endotracheal Secretions of Twin Patients. Pediatrics. 2016. PMID: 27418415
Beeton ML, Chalker VJ, Jones LC, Maxwell NC, Spiller OB. Antibiotic Resistance among Clinical Ureaplasma Isolates Recovered from Neonates in England and Wales between 2007 and 2013. Antimicrob Agents Chemother. 2015 Oct 12;60(1):52-6. doi: 10.1128/AAC.00889-15.
Alhusein N, Blagbrough IS, Beeton ML, Bolhuis A, De Bank PA. Electrospun Zein/PCL Fibrous Matrices Release Tetracycline in a Controlled Manner, Killing Staphylococcus aureus Both in Biofilms and Ex Vivo on Pig Skin, and are Compatible with Human Skin Cells. Pharm Res. 2016 Jan;33(1):237-46. doi: 10.1007/s11095-015-1782-3.
Mulley G, Beeton ML, Wilkinson P, Vlisidou I, Ockendon-Powell N, Hapeshi A, Tobias NJ, Nollmann FI, Bode HB, van den Elsen J, Ffrench-Constant RH, Waterfield NR.From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. PLoS One. 2015 Dec 17;10(12):e0144937. doi: 10.1371/journal.pone.0144937.
Beeton ML. Possible missed diagnosis of Ureaplasma spp infection in a case of fatal hyperammonemia after repeat renal transplantation. J Clin Anesth. 2015 Sep 28. pii: S0952-8180(15)00268-8. doi: 10.1016/j.jclinane.2015.08.019
Beeton ML, Alves DR, Enright MC, Jenkins AT. Assessing phage therapy against Pseudomonas aeruginosa using a Galleria mellonella infection model. Int J Antimicrob Agents. 2015 Aug;46(2):196-200. doi: 10.1016/j.ijantimicag.2015.04.005.
Nollmann FI, Heinrich AK, Brachmann AO, Morisseau C, Mukherjee K, Casanova-Torres ÁM, Strobl F, Kleinhans D, Kinski S, Schultz K, Beeton ML, Kaiser M, Chu YY, Phan Ke L, Thanwisai A, Bozhüyük KA, Chantratita N, Götz F, Waterfield NR, Vilcinskas A, Stelzer EH, Goodrich-Blair H, Hammock BD, Bode HB. A photorhabdus natural product inhibits insect juvenile hormone epoxide hydrolase. Chembiochem. 2015 Mar 23;16(5):766-71. doi: 10.1002/cbic.201402650.
Beeton ML, Aldrich-Wright JR, Bolhuis A. The antimicrobial and antibiofilm activities of copper(II) complexes. J Inorg Biochem. 2014 Nov;140:167-72. doi: 10.1016/j.jinorgbio.2014.07.012.
Beeton ML, Atkinson DJ, Waterfield NR. An amoeba phagocytosis model reveals a novel developmental switch in the insect pathogen Bacillus thuringiensis. J Insect Physiol. 2013 Feb;59(2):223-31. doi: 10.1016/j.jinsphys.2012.06.011.
Yang G, Hernández-Rodríguez CS, Beeton ML, Wilkinson P, Ffrench-Constant RH, Waterfield NR. Pdl1 is a putative lipase that enhances Photorhabdus toxin complex secretion. PLoS Pathog. 2012;8(5):e1002692. doi: 10.1371/journal.ppat.1002692.
Beeton ML, Daha MR, El-Shanawany T, Jolles SR, Kotecha S, Spiller OB. Serum killing of Ureaplasma parvum shows serovar-determined susceptibility for normal individuals and common variable immuno-deficiency patients. Immunobiology. 2012 Feb;217(2):187-94. doi: 10.1016/j.imbio.2011.07.009.
Beeton ML, Maxwell NC, Davies PL, Nuttall D, McGreal E, Chakraborty M, Spiller OB, Kotecha S. Role of pulmonary infection in the development of chronic lung disease of prematurity. Eur Respir J. 2011 Jun;37(6):1424-30. doi: 10.1183/09031936.00037810.
Davies PL, Spiller OB, Beeton ML, Maxwell NC, Remold-O'Donnell E, Kotecha S. Relationship of proteinases and proteinase inhibitors with microbial presence in chronic lung disease of prematurity. Thorax. 2010 Mar;65(3):246-51. doi: 10.1136/thx.2009.116061.
Beeton ML, Chalker VJ, Kotecha S, Spiller OB. 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. J Antimicrob Chemother. 2009 Sep;64(3):529-38. doi: 10.1093/jac/dkp218.
Beeton ML, Chalker VJ, Maxwell NC, Kotecha S, Spiller OB.Concurrent titration and determination of antibiotic resistance in ureaplasma species with identification of novel point mutations in genes associated with resistance. Antimicrob Agents Chemother. 2009 May;53(5):2020-7. doi: 10.1128/AAC.01349-08.
Dale C, Beeton M, Harbison C, Jones T, Pontes M. Isolation, pure culture, and characterization of "Candidatus Arsenophonus arthropodicus," an intracellular secondary endosymbiont from the hippoboscid louse fly Pseudolynchia canariensis. Appl Environ Microbiol. 2006 Apr;72(4):2997-3004.