Ashleigh Holmes
My research interests are in microbial pathogenicity, particularly in the regulation and expression of virulence factors.
Enterohaemorrhagic E. coli O157:H7 are important food-borne pathogens which colonise ruminants as commensals. Disease outbreaks are commonly associated with the consumption of contaminated meat or via direct contact, however a significant number have been attributed to the consumption of fresh produce (such as spinach, lettuce and radishes). During my PhD, I was interested in how type III secretion system effectors, particularly non-LEE encoded effectors, were regulated, expressed and how they contributed to this bacteria’s pathogenesis in mammals. Now, I am investigating the pathogenesis of E. coli O157:H7 in planta and the factors required for the bacterium’s interaction with plant tissues.
Current research interests
Oct 2011 – Sept 2014 BBSRC funded project: Identification and characterisation of EHEC adherence factors that interact with plant tissue.
There is mounting evidence that E. coli O157:H7 can utilise plants as hosts and not just as vectors for transmission. The mechanisms that the bacterium uses to exploit this niche are as yet not fully defined. The aim of this study is to identify bacterial surface-expressed factors that mediate the adherence of E. coli O157:H7 to plant roots.
Initial work has identified putative fimbriae which are involved in E. coli O157:H7 adherence to living plant roots, as demonstrated by adherence assays comparing mutants to wild-type parent strains. Using transcriptional fusions, the expression of these factors are increased at lower temperatures. The regulatory control of these factors at low temperature will also be defined.
Additional adherence factors will be identified and functionally characterized during the course of the project; with the intent to investigate whether they can also induce a plant immune defense response.
Past research
Oct 2007- Sept 2011 Medical Research Council funded PhD project at the University of Glasgow, supervised by Dr Andrew Roe and Professor Tim Mitchell: Characterising virulence factors from pathogenic bacteria using fluorescent reporters.
This research project aimed to understand the expression, secretion and localisation of two recently described non-LEE encoded (Nle) effector proteins thereby expanding our knowledge of the pathogenesis of EHEC. This was achieved by the construction fluorescent reporter fusions, western blotting, infection assays and fluorescence microscopy.
I also developed novel fluorescent reporters to investigate the expression and localization of virulence factors from the human pathogen Streptococcus pneumoniae.
Bibliography
- Waters, N.R.; Abram, F.; Brennan, F.; Holmes, A.; Pritchard, L. (2018) riboSeed: leveraging prokaryotic genomic architecture to assemble across ribosomal regions., Nucleic Acids Research, 46. Article No. e68.
- Wright, K.M.; Crozier, L.; Marshall, J.; Merget, B.; Holmes, A.; Holden, N.J. (2017) Differences in internalisation and growth of Escherichia coli O157:H7 within the apoplast of edible plants, spinach and lettuce, compared with the model species Nicotiana benthamiana., Microbial Biotechnology, 10, 555-569.
- Waters, N.R.; Abram, F.; Brennan, F.; Holmes, A.; Pritchard, L. (2017) riboSeed: leveraging prokaryotic genomic architecture to assemble across ribosomal regions., bioRxiv, Article No. 159798.
- Rossez, Y.; Wolfson, E.B.; Holmes, A.; Gally, D.L.; Holden, N.J. (2015) Bacterial flagella: twist and stick, or dodge across the Kingdoms., PLoS Pathogens, 11, Article No. e1004483.
- Holden, N.J.; Holmes, A.; Rossez, Y. (2015) The molecular interactions between human pathogenic bacteria and plants., In: Murillo, J., Vinatzer, B.A., Jackson, R.W. & Arnold, D.L. (eds.). Bacteria-Plant Interactions: Advanced Research and Future Trends, Caister Academic Press, pp139-166.
- Holmes, A.; Birse, L.; Jackson, R.W.; Holden, N.J. (2014) An optimised method for the extraction of bacterial mRNA from plant roots infected with Escherichia coli O157:H7., Frontiers in Microbiology, 5, Article No. 286.
- Rossez, Y.; Holmes, A.; Lodberg-Pedersen, H.; Birse, L.; Marshall, J.; Willats, W.G.T.; Toth, I.K.; Holden, N.J. (2014) Escherichia coli common pilus (ECP) targets arabinosyl residues in plant cell walls to mediate adhesion to fresh produce plants., Journal of Biological Chemistry, 289, 34349-34365.
- Bewley, M.A.; Naughton, M.; Preston, J.; Mitchell, A.; Holmes, A.; Marriott, H.M.; Read, R.C.; Mitchell, T.J.; Whyte, M.K.B.; Dockrell, D.H. (2014) Pneumolysin activates macrophage lysosomal membrane permeabilization and executes apoptosis by distinct mechanisms without membrane pore formation., mBio, 5, Article No. e01710-14.
- Rossez, Y.; Holmes, A.; Wolfson, W.B.; Gally, D.L.; Mahjan, A.; Pedersen, H.L.; Willats, W.G.T.; Toth, I.K.; Holden, N. (2014) Flagella interact with ionic plant lipids to mediate adherence of pathogenic Escherichia coli to fresh produce plants., Environmental Microbiology, 16, 2181-2195.
- Waters, N.R.; Abram, F.; Brennan, F.; Holmes, A.; Pritchard, L. (2018) riboSeed: leveraging prokaryotic genomic architecture to assemble across ribosomal regions., Nucleic Acids Research, 46. Article No. e68.
- Wright, K.M.; Crozier, L.; Marshall, J.; Merget, B.; Holmes, A.; Holden, N.J. (2017) Differences in internalisation and growth of Escherichia coli O157:H7 within the apoplast of edible plants, spinach and lettuce, compared with the model species Nicotiana benthamiana., Microbial Biotechnology, 10, 555-569.
- Waters, N.R.; Abram, F.; Brennan, F.; Holmes, A.; Pritchard, L. (2017) riboSeed: leveraging prokaryotic genomic architecture to assemble across ribosomal regions., bioRxiv, Article No. 159798.
- Rossez, Y.; Wolfson, E.B.; Holmes, A.; Gally, D.L.; Holden, N.J. (2015) Bacterial flagella: twist and stick, or dodge across the Kingdoms., PLoS Pathogens, 11, Article No. e1004483.
- Holmes, A.; Birse, L.; Jackson, R.W.; Holden, N.J. (2014) An optimised method for the extraction of bacterial mRNA from plant roots infected with Escherichia coli O157:H7., Frontiers in Microbiology, 5, Article No. 286.
- Rossez, Y.; Holmes, A.; Lodberg-Pedersen, H.; Birse, L.; Marshall, J.; Willats, W.G.T.; Toth, I.K.; Holden, N.J. (2014) Escherichia coli common pilus (ECP) targets arabinosyl residues in plant cell walls to mediate adhesion to fresh produce plants., Journal of Biological Chemistry, 289, 34349-34365.
- Bewley, M.A.; Naughton, M.; Preston, J.; Mitchell, A.; Holmes, A.; Marriott, H.M.; Read, R.C.; Mitchell, T.J.; Whyte, M.K.B.; Dockrell, D.H. (2014) Pneumolysin activates macrophage lysosomal membrane permeabilization and executes apoptosis by distinct mechanisms without membrane pore formation., mBio, 5, Article No. e01710-14.
- Rossez, Y.; Holmes, A.; Wolfson, W.B.; Gally, D.L.; Mahjan, A.; Pedersen, H.L.; Willats, W.G.T.; Toth, I.K.; Holden, N. (2014) Flagella interact with ionic plant lipids to mediate adherence of pathogenic Escherichia coli to fresh produce plants., Environmental Microbiology, 16, 2181-2195.
- Holden, N.J.; Holmes, A.; Rossez, Y. (2015) The molecular interactions between human pathogenic bacteria and plants., In: Murillo, J., Vinatzer, B.A., Jackson, R.W. & Arnold, D.L. (eds.). Bacteria-Plant Interactions: Advanced Research and Future Trends, Caister Academic Press, pp139-166.
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