Dr C. Jane Dixon

Job: Senior Lecturer

Faculty: Health and Life Sciences

School/department: Leicester School of Pharmacy

Research group(s): Pharmacology

Address: De Montfort University, The Gateway, Leicester, LE1 9BH

T: +44 (0)116 207 8117

E: jdixon@dmu.ac.uk

W: http://dmu.ac.uk/hls

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Publications and outputs

Gene expression analysis of transport channels in Enterococcus faecium (VRE)
Gene expression analysis of transport channels in Enterococcus faecium (VRE) Al hareth, Zakia; Owen, L.; Dixon, C. J.; Smith, L. M.; Laird, Katie Introduction: An important aspect of the bacterial response towards stress and environmental stimuli is alteration of gene expression levels . A combination of carvacrol, cuminaldehyde, and vancomycin has previously been shown to re-sensitise vancomycin-resistant E. faecium (VRE) to vancomycin . The effect of treatment with the novel antimicrobial combination for 60minutes on gene expression in VRE was analysed by microarray analysis. Microarray data showed that 15 genes were differentially regulated and five genes associated with transport channels were chosen for further analysis; bcr, ecfa_1, ecsa1, ylob, and nhac_2. A time course study using qPCR was conducted to further understand the antimicrobial mechanism of action of the novel formula. Methods: qPCR was carried out to validate the microarray data at 60mins. In addition, alterations in the expression levels of the five genes were assessed at 10mins, 30mins, 2hrs and 6hrs, in response to cuminaldehyde and carvacrol alone, in combination, and in combination with the vancomycin. Results: VRE responds to the novel formula in the initial stages of exposure; at 10mins significant changes (p≤0.05) were demonstrated in the expression of the five genes, bcr, ecfa_1, ecsa_1, ylob, nhac_2 with fold changes of -13.5, -1.41, -3.95, -5.67, and -6.31 respectively. At 60mins only nhac_2 showed a significant fold change of -3.09. At 2hrs there were significant fold changes for bcr at 15.03, ecfa-1 at 2.85 and nhac_2 at 4.7, whereas at 6hrs there were no significant changes for any of the five genes tested. Conclusion: This study has demonstrated that treating VRE with EOs alone and in combination with vancomycin has resulted in fold changes in the expression levels of the transport genes of interest. A new EO-vancomycin formulation to combat VRE could be developed through exploiting transport channels in Enterococcus sp.
The mechanism of antibacterial action of Essential Oils against Enterococcus faecium: the role of transport channels
The mechanism of antibacterial action of Essential Oils against Enterococcus faecium: the role of transport channels Alhareth, Z; Owen, L.; Dixon, C. J.; McKechnie, K.; Laird, Katie; Smith, I. Aims The overall aim of this study is to establish the mechanisms of action of a novel formulation of plant extracts known to be effective against Vancomycin Resistant E. faecium (VRE) isolates. Channels in the bacterial cell wall were assessed to see if they act in a similar way to mammalian cell Transient Receptor Potential Channels (TRPV1) that are known to be activated by the EOs and capsaicin. Methods and results Growth curves and viable counts were conducted for E. faecium (VSE) in the presence of the TRPV1 channel blocker AMG517, EO blend (carvacrol 0.2µl and cuminaldehyde 25µl) and capsaicin. Microarray data was used to assess which genes associated with ion channels were differentially regulated in the presence of EO blend. AMG517 (10nM to 90nM) did not limit the inhibitory effect of capsaicin (Minimum Inhibitory Concentration:1.6mM) or the EO blend on E. faecium. This suggests that a homologue of TRPV1 does not exist in E. faecium. Microarray data showed that there are genes encoding channels including kup, bcr, gsia_1, mscL, gla_2, ylob that were differentially regulated when exposed to the EO blend. Conclusions The microarray data suggests that cell wall channels are involved in the mechanism of action of EOs; despite the antimicrobial action of capsaicin on E. faecium results are not consistent with the involvement of TRPV1 homologue in bacteria. Significance of study Due to an increase in antibiotic resistance, novel antimicrobial compounds with mechanisms of action that are effective against multi-drug resistant (MDR) microorganisms are of particular interest1,2. Although a homologue of TRPV1 was not identified, microarray data demonstrates that the EO blend is having an effect on genes involved in transport mechanisms. Further investigations are required to ascertain the exact mechanism of action of EOs against bacteria in order for them to be exploited as novel antimicrobials. References 1. Wikaningtyas P, Sukandar EY. The antibacterial activity of selected plants towards resistant bacteria isolated from clinical specimens. Asian Pac J Trop Biomed. 2016;6(1):16-19. doi:10.1016/j.apjtb.2015.08.003 2. Simpkin VL, Renwick MJ, Kelly R, Mossialos E. Incentivising innovation in antibiotic drug discovery and development: Progress, challenges and next steps. J Antibiot (Tokyo). 2017;70(12):1087-1096. doi:10.1038/ja.2017.124
Can H2-receptor upregulation and raised histamine explain an anaphylactoid reaction on cessation of ranitidine in a 19 year old female?
Can H2-receptor upregulation and raised histamine explain an anaphylactoid reaction on cessation of ranitidine in a 19 year old female? Allen, Susan; Dixon, C. J.; Chazot P L The anaphylactoid reaction described follows cessation of ranitidine in a 19 year old female with the disease cluster: mast cell activation syndrome, hypermobile Ehlers-Danlos syndrome and postural tachycardia syndrome. Anaphylaxis can give wide-ranging symptoms, from rhinorrhea and urticaria to tachycardia and system-wide, life-threatening, anaphylactic shock. Individuals with a disorder of mast cell activation can experience many such symptoms. H2 receptor antagonists, such as ranitidine, are commonly prescribed in this population. A mechanism for the reaction is proposed in the context of ranitidine, as an inverse agonist, causing upregulation of H2 histamine receptors and raised histamine levels due to enzyme induction. This effect, following extended and/or high antihistamine dosing, may have implications for other individuals with a disorder of mast cell activation, such as mastocytosis or mast cell activation syndrome. There are potential policy and patient guidance implications for primary and secondary care with respect to cessation of H2 antagonists. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
Is the antimicrobial mechanism of action of essential oils against bacteria associated with channels similar to TRPV1 channels found in mammalian cells?
Is the antimicrobial mechanism of action of essential oils against bacteria associated with channels similar to TRPV1 channels found in mammalian cells? Alhareth, Z; Owen, L.; Dixon, C. J.; McKechnie, K.; Smith, Laura J.; Laird, Katie Objectives: The aim of this investigation was to find out if the antimicrobial mechanism of action of Essential Oils (EOs) against Enterococcus spp. may be associated with channels similar to TRPV1 channels found in mammalian cells. A known antimicrobial combination of EOs compounds (Carvacrol 0.2µl and Cuminaldehyde 25µl) against E. faecium and capsaicin were used to investigate this hypothesis. The bacterial membrane has many porin proteins which act as hydrophilic transmembrane channels and allow small hydrophilic solutes to pass through them1, such channels may be the target for the antimicrobial mechanism of action of EOs in the Gram-positive bacterial cell wall. Methods: Transient receptor potential (TRP) channels, are a group of unique ion channels in mammalian cells, that are effected by a wide spectrum of physical and chemical stimuli2, including high temperature and low pH. Capsaicin the EO compound of chilli peppers is known to be a TRP channel antagonist in mammalian cells2,3 whilst AMG 517 specifically blocks TRP channels, and Ruthenium Red (RR) is a wide spectrum blocker for TRPV1 channels4,5. The Minimum Inhibitory Concentration (MIC) of capsaicin against Vancomycin Sensitive E. faecium (VSE) was defined by agar-broth dilution method, a checkerboard assay was conducted to determine the interactions of AMG517 and RR against E. faecium. A growth curve was also conducted to assess the effect of the EO blend in the presence of AMG517. Results: Capsaicin showed antibacterial activity against E. faecium with an MIC of 1.6mM. The checkerboard data demonstrated that AMG517 has no inhibitory effect on E. faecium and therefore was a good candidate to reverse the effect of EOs blend by potentially blocking channels that were similar to TRPV1. RR was antimicrobial at concentrations above 10µM, however, AMG517 above 60nM reverses the inhibitory effect of RR, demonstrating a competitive effect of AMG517 and RR towards a definite site in the bacterial cell wall. Growth curves showed no reverse effect of the EO blend in the presence of AMG517. Conclusions: This study does not support the existence of a TRPVI homologue in the bacterial cell. Future studies will investigate the genes related to transport channels in E. faecium, that are differentially regulated when exposed to the EO blend, in order to further understand the effect of the EOs on transport channels in bacteria.
Pharmacology for Pharmacy and the Health Sciences
Pharmacology for Pharmacy and the Health Sciences Boarder, M. R.; Dixon, C. J.; Newby, D; Navti, P; Zetterstrom, T. S. C.
Endosomal signalling of epidermal growth factor receptors contributes to EGF-stimulated cell cycle progression in primary hepatocytes.
Endosomal signalling of epidermal growth factor receptors contributes to EGF-stimulated cell cycle progression in primary hepatocytes. Luo, Y.; Cheng, Z.; Dixon, C. J.; Hall, J. F.; Taylor, E.; Boarder, M. R.
Establishing the stochastic nature of intracellular calcium oscillations from experimental data
Establishing the stochastic nature of intracellular calcium oscillations from experimental data Perc, M.; Green, A. K.; Dixon, C. J.; Marhl, M.
Information transfer in signaling pathways: A study using coupled simulated and experimental data
Information transfer in signaling pathways: A study using coupled simulated and experimental data Pahle, J.; Green, A. K.; Dixon, C. J.; Kummer, U.
Spatio-temporal modelling explains the effect if reduced plasma membrane Ca2+ efflux on intracellular Ca2+ oscillations in hepatocytes
Spatio-temporal modelling explains the effect if reduced plasma membrane Ca2+ efflux on intracellular Ca2+ oscillations in hepatocytes Marhl, M.; Gosak, M.; Perc, M.; Dixon, C. J.; Green, A. K.
A role for Akt in EGF-stimulated cell cycle progression in cultured hepatocytes: generation of a hyperproliferative window following adenoviral expression of constitutively active Akt
A role for Akt in EGF-stimulated cell cycle progression in cultured hepatocytes: generation of a hyperproliferative window following adenoviral expression of constitutively active Akt Boarder, M. R.; Luo, Y.; Dixon, C. J.; Hall, J. F.; White, Pamela J.

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Research interests/expertise

Cell Biology
Cell Signalling

Conference attendance

UK Purine Club Meeting - Invited talk 17/09/2010

Current research students

Sarah Williams PhD - First Supervisor

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