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Dr Alan Brown

Dr Alan Brown

Senior Lecturer in Molecular Microbiology

 5526

 +44 (0)1392 725526

 Geoffrey Pope 404

 

Geoffrey Pope Building, University of Exeter , Stocker Road, Exeter, EX4 4QD, UK

I am a molecular microbiologist interested in mechanisms of virulence and niche adaptation in pathogenic bacteria. Research programmes within my group are focused on defining how such mechanisms impact on host-microbe interactions during infection, with the aim of using this knowledge to guide the rational development of novel antimicrobial strategies.

I am a member of the Microbes and Disease research group.

 

 

Qualifications

2010 Postgraduate Certificate in Academic Practice, University of Exeter

2001 PhD, University of Edinburgh

1997 BSc (Hons) Medical Microbiology, University of Edinburgh

Career

2013-Present  Senior Lecturer in Molecular Microbiology, School of Biosciences, University of Exeter

2008-2013  Lecturer in Molecular Microbiology, School of Biosciences, University of Exeter
2005-2008  Postdoctoral Fellow & Coordinator of the UK Cystic Fibrosis Microbiology Consortium, Centre for Infectious Diseases, University of Edinburgh
2003-2005  Postdoctoral Scientist, The Roslin Institute
2000-2003  Postdoctoral Research Associate, Dept. of Veterinary Pathology, University of Edinburgh

 

Research

Research interests

 My research primarily focuses on Pseudomonas aeruginosa and species of the Burkholderia genus, specifically Burkholderia pseudomallei and members of the Burkholderia cepacia complex (Bcc). P. aeruginosa and the Bcc are both formidable pathogens of the cystic fibrosis (CF) lung, whilst P. aeruginosa is also a significant cause of healthcare-associated infection. In contrast, B. pseudomallei is the causative agent of melioidosis, a disease which is endemic in parts of southeast Asia and northern Australia.

I am interested in the fundamental mechanisms that underlie the virulence of these organisms, how genome and transcriptome plasticity facilitates their adaptation to diverse niches, and how knowledge of these processes can guide the development of novel therapeutic strategies.

 

Research projects

1.  Investigating the role and inter-connectedness of metal-responsive two-component systems.

Bacteria possess efficient mechanisms by which they can sense and respond to heavy metals, including zinc, silver and copper. These mechanisms frequently involve two-component systems (TCSs), which sense the extracellular environment and trigger an appropriate response (typically a transcriptional response). We are exploring such metal-responsive TCSs in Burkholderia and Pseudomonas species, investigating their role in metal resistance and the extent to which these systems are interconnected.

 

2.  The sphingosine-1-phosphate axis in host-microbe interactions.

In collaboration with Prof. Dominic Campopiano of the University of Edinburgh's School of Chemistry, we have identified that B. pseudomallei encodes two putative sphingosine-1-phosphate lyase (S1PL) enzymes that irreversibly degrade sphingosine-1-phosphate (S1P). In mammals, S1P is an important bioactive sphingolipid metabolite with diverse roles in numerous pathways including the regulation of immune and inflammatory processes. We are investigating the role of these bacterial-encoded S1PLs in virulence and immune evasion. In addition, we are investigating whether therapeutic targeting of the S1P axis represents a viable immunomodulatory-based anti-infective strategy.

 

3.  Epidemiology of P. aeruginosa in CF and non-CF bronchiectasis patients.

In collaboration with clinical colleagues at the Royal Devon & Exeter Hospital, we are assessing the epidemiology of P. aeruginosa in bronchiectasis patients (CF and non-CF). In addition, we aim to determine whether individual patients harbour multiple strains of P. aeruginosa and also assess the wider microbial diversity within non-CF bronchiectasis patients.

 

In addition, other research interests include:

  • The interconnectedness and relative hierarchies of gene regulatory networks in P. aeruginosa;
  • How members of the Bcc adapt during chronic infection of the CF airways, and how such adaptations impact on the host-pathogen interaction and ultimately the progression of disease.

 

Research networks

  • Dr Steve Porter, University of Exeter
  • Prof. Eshwar Mahenthiralingam, Cardiff University
  • Dr Dominic Campopiano, University of Edinburgh
  • Prof. Aras Kadioglu, University of Liverpool
  • Dr Chris Sheldon, Royal Devon & Exeter Hospital
  • Dr Nick Withers, Royal Devon & Exeter Hospital
  • Prof. John Govan, University of Edinburgh
  • Prof. Miguel Valvano, Queen's University Belfast
  • Dr Mitali Sarkar-Tyson, DSTL
  • Prof. Paul Williams, University of Nottingham
  • Prof. Anne Dell, Imperial College London

Research grants

  • 2012 BBSRC
    Pseudomonas quinolone signal and two-component systems; Unravelling the intricate network of gene regulation in Pseudomonas aeruginosa
  • 2010 The Cystic Fibrosis Trust
    'The impact of diabetes on the microbiology of cystic fibrosis lung disease'
  • 2010 Royal Society
    Characterizing the aminoarabinose biosynthetic pathway of the Burkholderia genus; An Achilles� heel of a multi-resistant bacterial pathogen & biowarfare agent?
  • 2008 MRC
    New Investigator Research Grant 'Novel transcriptional regulators of virulence in the genus Burkholderia'

Key publications | Publications by category | Publications by year

Key publications


Custódio R, McLean CJ, Scott AE, Lowther J, Kennedy A, Clarke DJ, Campopiano DJ, Sarkar-Tyson M, Brown AR (In Press). Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei. Mol Microbiol, 102(6), 1004-1019. Abstract.  Author URL.  Full text.
Francis V, Waters EM, Finton-James SE, Gori A, Kadioglu A, Brown A, Porter SL (2018). Multiple communication mechanisms between sensor kinases are crucial for virulence in Pseudomonas aeruginosa. Nature Communications, 9, 2219-2219. Full text.
McLean CJ, Marles-Wright J, Custodio R, Lowther J, Kennedy AJ, Pollock J, Clarke DJ, Brown AR, Campopiano DJ (2017). Characterization of homologous sphingosine-1- phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei. Journal of Lipid Research, 58(1), 137-150. Abstract.  Full text.
Mitchelmore PJ, Randall J, Bull MJ, Moore KA, O'Neill PA, Paszkiewicz K, Mahenthiralingam E, Scotton CJ, Sheldon CD, Withers NJ, et al (2017). Molecular epidemiology of Pseudomonas aeruginosa in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort. Thorax Abstract.  Author URL.  Full text.
Denman CC, Robinson MT, Sass AM, Mahenthiralingam E, Brown AR (2014). Growth on mannitol-rich media elicits a genomewide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner. Microbiology (United Kingdom), 160(PART 1), 187-197. Abstract.
Denman CC, Brown AR (2013). Mannitol promotes adherence of an outbreak strain of Burkholderia multivorans via an exopolysaccharide-independent mechanism that is associated with upregulation of newly identified fimbrial and afimbrial adhesins. Microbiology (United Kingdom), 159(4), 771-781. Abstract.

Publications by category


Journal articles

Custódio R, McLean CJ, Scott AE, Lowther J, Kennedy A, Clarke DJ, Campopiano DJ, Sarkar-Tyson M, Brown AR (In Press). Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei. Mol Microbiol, 102(6), 1004-1019. Abstract.  Author URL.  Full text.
Francis V, Waters EM, Finton-James SE, Gori A, Kadioglu A, Brown A, Porter SL (2018). Multiple communication mechanisms between sensor kinases are crucial for virulence in Pseudomonas aeruginosa. Nature Communications, 9, 2219-2219. Full text.
McLean CJ, Marles-Wright J, Custodio R, Lowther J, Kennedy AJ, Pollock J, Clarke DJ, Brown AR, Campopiano DJ (2017). Characterization of homologous sphingosine-1- phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei. Journal of Lipid Research, 58(1), 137-150. Abstract.  Full text.
Mitchelmore PJ, Randall J, Bull MJ, Moore KA, O'Neill PA, Paszkiewicz K, Mahenthiralingam E, Scotton CJ, Sheldon CD, Withers NJ, et al (2017). Molecular epidemiology of Pseudomonas aeruginosa in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort. Thorax Abstract.  Author URL.  Full text.
Kilonzo-Nthenge A, Brown A, Nahashon SN, Long D (2015). Occurrence and antimicrobial resistance of enterococci isolated from organic and conventional retail chicken. Journal of Food Protection, 78(4), 760-766. Abstract.
Denman CC, Robinson MT, Sass AM, Mahenthiralingam E, Brown AR (2014). Growth on mannitol-rich media elicits a genomewide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner. Microbiology (United Kingdom), 160(PART 1), 187-197. Abstract.
Denman CC, Brown AR (2013). Mannitol promotes adherence of an outbreak strain of Burkholderia multivorans via an exopolysaccharide-independent mechanism that is associated with upregulation of newly identified fimbrial and afimbrial adhesins. Microbiology (United Kingdom), 159(4), 771-781. Abstract.
Clarke DJ, Ortega XP, Mackay CL, Valvano MA, Govan JRW, Campopiano DJ, Langridge-Smith P, Brown AR (2010). Subdivision of the bacterioferritin comigratory protein family of bacterial peroxiredoxins based on catalytic activity. Biochemistry, 49(6), 1319-1330. Abstract.  Full text.
Clarke DJ, Mackay CL, Campopiano DJ, Langridge-Smith P, Brown AR (2009). Interrogating the molecular details of the peroxiredoxin activity of the Escherichia coli bacterioferritin comigratory protein using high-resolution mass spectrometry. Biochemistry, 48(18), 3904-3914. Abstract.  Author URL.  Full text.
Bartholdson SJ, Brown AR, Mewburn BR, Clarke DJ, Fry SC, Campopiano DJ, Govan JR (2008). Plant host and sugar alcohol induced exopolysaccharide biosynthesis in the Burkholderia cepacia complex. Microbiology, 154(Pt 8), 2513-2521. Abstract.  Full text.
Ortega XP, Cardona ST, Brown AR, Loutet SA, Flannagan RS, Campopiano DJ, Govan JR, Valvano MA (2007). A putative gene cluster for aminoarabinose biosynthesis is essential for Burkholderia cenocepacia viability. J Bacteriol., 189(9), 3639-3644. Abstract.
Brown AR, Govan JRW (2007). Assessment of fluorescent in situ hybridization and PCR-based methods for rapid identification of Burkholderia cepacia complex organisms directly from sputum samples. J Clin Microbiol, 45(6), 1920-1926. Abstract.  Author URL.
Brown AR, Blanco ARA, Miele G, Hawkins SA, Hopkins J, Fazakerley JK, Manson J, Clinton M (2007). Differential expression of erythroid genes in prion disease. Biochem Biophys Res Commun, 364(2), 366-371. Abstract.  Author URL.
Govan JRW, Brown AR, Jones AM (2007). Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection. Future Microbiol, 2(2), 153-164. Abstract.  Author URL.
Brown AR, Rebus S, McKimmie CS, Robertson K, Williams A, Fazakerley JK (2005). Gene expression profiling of the preclinical scrapie-infected hippocampus. Biochem Biophys Res Commun, 334(1), 86-95. Abstract.  Author URL.
Brown AR, Webb J, Rebus S, Williams A, Fazakerley JK (2004). Identification of up-regulated genes by array analysis in scrapie-infected mouse brains. Neuropathol Appl Neurobiol, 30(5), 555-567. Abstract.  Author URL.
Brown AR, Webb J, Rebus S, Walker R, Williams A, Fazakerley JK (2003). Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease. J Gen Virol, 84(Pt 9), 2605-2611. Abstract.  Author URL.
Brown AR, Townsley AC, Amyes SG (2001). Diversity of Tn1546 elements in clinical isolates of glycopeptide-resistant enterococci from Scottish hospitals. Antimicrob Agents Chemother, 45(4), 1309-1311. Abstract.  Author URL.
Nelson RR, McGregor KF, Brown AR, Amyes SG, Young H (2000). Isolation and characterization of glycopeptide-resistant enterococci from hospitalized patients over a 30-month period. J Clin.Microbiol., 38(6), 2112-2116. Abstract.
Brown AR, Amyes SG, Paton R, Plant WD, Stevenson GM, Winney RJ, Miles RS (1998). Epidemiology and control of vancomycin-resistant enterococci (VRE) in a renal unit. J Hosp.Infect., 40(2), 115-124. Abstract.

Publications by year


In Press

Custódio R, McLean CJ, Scott AE, Lowther J, Kennedy A, Clarke DJ, Campopiano DJ, Sarkar-Tyson M, Brown AR (In Press). Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei. Mol Microbiol, 102(6), 1004-1019. Abstract.  Author URL.  Full text.

2018

Francis V, Waters EM, Finton-James SE, Gori A, Kadioglu A, Brown A, Porter SL (2018). Multiple communication mechanisms between sensor kinases are crucial for virulence in Pseudomonas aeruginosa. Nature Communications, 9, 2219-2219. Full text.

2017

McLean CJ, Marles-Wright J, Custodio R, Lowther J, Kennedy AJ, Pollock J, Clarke DJ, Brown AR, Campopiano DJ (2017). Characterization of homologous sphingosine-1- phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei. Journal of Lipid Research, 58(1), 137-150. Abstract.  Full text.
Mitchelmore PJ, Randall J, Bull MJ, Moore KA, O'Neill PA, Paszkiewicz K, Mahenthiralingam E, Scotton CJ, Sheldon CD, Withers NJ, et al (2017). Molecular epidemiology of Pseudomonas aeruginosa in an unsegregated bronchiectasis cohort sharing hospital facilities with a cystic fibrosis cohort. Thorax Abstract.  Author URL.  Full text.

2015

Kilonzo-Nthenge A, Brown A, Nahashon SN, Long D (2015). Occurrence and antimicrobial resistance of enterococci isolated from organic and conventional retail chicken. Journal of Food Protection, 78(4), 760-766. Abstract.

2014

Denman CC, Robinson MT, Sass AM, Mahenthiralingam E, Brown AR (2014). Growth on mannitol-rich media elicits a genomewide transcriptional response in Burkholderia multivorans that impacts on multiple virulence traits in an exopolysaccharide-independent manner. Microbiology (United Kingdom), 160(PART 1), 187-197. Abstract.

2013

Denman CC, Brown AR (2013). Mannitol promotes adherence of an outbreak strain of Burkholderia multivorans via an exopolysaccharide-independent mechanism that is associated with upregulation of newly identified fimbrial and afimbrial adhesins. Microbiology (United Kingdom), 159(4), 771-781. Abstract.

2010

Clarke DJ, Ortega XP, Mackay CL, Valvano MA, Govan JRW, Campopiano DJ, Langridge-Smith P, Brown AR (2010). Subdivision of the bacterioferritin comigratory protein family of bacterial peroxiredoxins based on catalytic activity. Biochemistry, 49(6), 1319-1330. Abstract.  Full text.

2009

Clarke DJ, Mackay CL, Campopiano DJ, Langridge-Smith P, Brown AR (2009). Interrogating the molecular details of the peroxiredoxin activity of the Escherichia coli bacterioferritin comigratory protein using high-resolution mass spectrometry. Biochemistry, 48(18), 3904-3914. Abstract.  Author URL.  Full text.

2008

Bartholdson SJ, Brown AR, Mewburn BR, Clarke DJ, Fry SC, Campopiano DJ, Govan JR (2008). Plant host and sugar alcohol induced exopolysaccharide biosynthesis in the Burkholderia cepacia complex. Microbiology, 154(Pt 8), 2513-2521. Abstract.  Full text.

2007

Ortega XP, Cardona ST, Brown AR, Loutet SA, Flannagan RS, Campopiano DJ, Govan JR, Valvano MA (2007). A putative gene cluster for aminoarabinose biosynthesis is essential for Burkholderia cenocepacia viability. J Bacteriol., 189(9), 3639-3644. Abstract.
Brown AR, Govan JRW (2007). Assessment of fluorescent in situ hybridization and PCR-based methods for rapid identification of Burkholderia cepacia complex organisms directly from sputum samples. J Clin Microbiol, 45(6), 1920-1926. Abstract.  Author URL.
Brown AR, Blanco ARA, Miele G, Hawkins SA, Hopkins J, Fazakerley JK, Manson J, Clinton M (2007). Differential expression of erythroid genes in prion disease. Biochem Biophys Res Commun, 364(2), 366-371. Abstract.  Author URL.
Govan JRW, Brown AR, Jones AM (2007). Evolving epidemiology of Pseudomonas aeruginosa and the Burkholderia cepacia complex in cystic fibrosis lung infection. Future Microbiol, 2(2), 153-164. Abstract.  Author URL.

2005

Brown AR, Rebus S, McKimmie CS, Robertson K, Williams A, Fazakerley JK (2005). Gene expression profiling of the preclinical scrapie-infected hippocampus. Biochem Biophys Res Commun, 334(1), 86-95. Abstract.  Author URL.

2004

Brown AR, Webb J, Rebus S, Williams A, Fazakerley JK (2004). Identification of up-regulated genes by array analysis in scrapie-infected mouse brains. Neuropathol Appl Neurobiol, 30(5), 555-567. Abstract.  Author URL.

2003

Brown AR, Webb J, Rebus S, Walker R, Williams A, Fazakerley JK (2003). Inducible cytokine gene expression in the brain in the ME7/CV mouse model of scrapie is highly restricted, is at a strikingly low level relative to the degree of gliosis and occurs only late in disease. J Gen Virol, 84(Pt 9), 2605-2611. Abstract.  Author URL.

2001

Brown AR, Townsley AC, Amyes SG (2001). Diversity of Tn1546 elements in clinical isolates of glycopeptide-resistant enterococci from Scottish hospitals. Antimicrob Agents Chemother, 45(4), 1309-1311. Abstract.  Author URL.

2000

Nelson RR, McGregor KF, Brown AR, Amyes SG, Young H (2000). Isolation and characterization of glycopeptide-resistant enterococci from hospitalized patients over a 30-month period. J Clin.Microbiol., 38(6), 2112-2116. Abstract.

1998

Brown AR, Amyes SG, Paton R, Plant WD, Stevenson GM, Winney RJ, Miles RS (1998). Epidemiology and control of vancomycin-resistant enterococci (VRE) in a renal unit. J Hosp.Infect., 40(2), 115-124. Abstract.

alan_brown Details from cache as at 2018-10-15 04:08:05

Refresh publications

Invited lectures

2015. Giving the host the slip: The role of sphingosine-1-phosphate lyases (S1PL) of Burkholderia pseudomallei. OnE Seminar Series, University of Cardiff. 

2009. The evolving epidemiology of Burkholderia cepacia complex in CF lung infection: The 'B. multivorans story'. Presented at the Scottish Cystic Fibrosis Group Meeting, Stirling.

2009. Mechanisms of virulence and niche adaptation in the genus Burkholderia. University of Newcastle (Transplantation and Immunobiology Research Group meeting).


Workshops/Conferences organised

2009. Organising Committee for the 2nd South West and South Wales Regional Microbiology Forum, Exeter, 24th Sep 2009.

2005-2008. Coordinator of the UK Cystic Fibrosis Microbiology Consortium.

I am a Fellow of the Higher Education Academy.

I contribute to the following modules:

Level 2.

  • BIO2089 – Molecular Biology of the Gene
  • BIO2094 - Molecular Microbiology (module coordinator)

Level 3.

  • BIO3079 – Molecular Basis of Infection (module coordinator)

 

I am also Senior Programme Advisor for the Human Biosciences degree programme.

Postgraduate researchers

Alumni

  • Dr Rafael Custodio
  • Dr Carmen Denman
  • Dr Philip Mitchelmore
  • Dr Matthew Robinson

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