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Professor Eshwar Mahenthiralingam

Professor Eshwar Mahenthiralingam

Co-Director of Research

School of Biosciences

Email:
mahenthiralingame@cardiff.ac.uk
Telephone:
+44 (0)29 2087 5875
Fax:
+44 (0)29 2087 4305
Location:
West 2.06, Sir Martin Evans Building, Museum Avenue, Cardiff, CF10 3AX
Available for postgraduate supervision

Research overview

My group has studied the pathogenesis and ecology of bacterial opportunistic pathogens, ranging from Pseudomonas aeruginosa to mycobacteria, with a major focus on Burkholderia cepacia complex bacteria. Pseudomonas and Burkholderia bacteria cause devastating infections in people with cystic fibrosis and we have used molecular biology and genomic approaches to track their ability to spread between patients, resist killing by antibiotics and cause lung disease. Since both these bacteria are also important in the natural environment, we have also studied several aspects of their ecology. By understanding the complete biology of opportunistic bacterial pathogens in this way we hope to develop strategies to both treat human infection and also harness their considerable biotechnological potential. Our recent discoveries that Burkholderia bacteria produce a range of antibiotics that target resistant infections and plant pathogens are very exciting.

Microbiomes, Microbes and Informatics

The Mahenthiralingam group is part of the recently formed Microbiomes, Microbes and Informatics (MMI) group (webpage underdevelopment). The MMI group currently comprises the research groups of Cedric Berger, Thomas Connor, Esh Mahenthiralingam, Julian Marchesi and Andrew Weightman, and has over 25 active research staff and postgraduate students. The MMI group welcomes approaches by potential fellowship applicants and funded PhD students to host their research and expand our strategic research on Microbiomes, Microbes and Informatics.

I was born in Penang, Malaysia, but grew up as a "Brummy" in Walsall, West Midlands, UK. My undergraduate studies (B.Sc. in Applied Biology; 1987) were completed at the then University of Wales Institute of Science and Technology, which subsequently became part of Cardiff University.  I completed a Ph.D. (Molecular Microbiology; 1991) at the Medical Research Council's National Institute for Medical Research at Mill Hill, London, working on mycobacteria, the bacteria most known for causing tuberculosis.

After my PhD, I took up a postdoctoral position (1991) at the Faculty of Medicine, University of British Columbia, Vancouver, Canada. This is where I began to developing expertise in the cystic fibrosis microbiology, working on Pseudomonas aeruginosa and Burkholderia cepacia complex bacteria that cause devastating lung infections in these individuals. The two year postdoctoral position turned into a nine year stay, that included obtaining a Fellowship from the Canadian Cystic Fibrosis Foundation, moving through several positions, with a final appointment as an Associate Professor in 1997.

In June 1999, I joined Cardiff School of Biosciences, Cardiff University, as a Lecturer, returning to Wales and the institution I had first studied within. I served on the editorial board of the Journal of Clinical Microbiology from 2000 to 2008, and continue to guest review for the American Society for Microbiology journals as well as many other science journals and grant funding bodies. In August, 2011, after previous promotions to Senior Lecturer (2004), and Reader (2007), I was promoted to Professor. I currently serve as the Postgraduate Tutor for the Organisms and Environment Division and coordinate the final year module "Human Infectious Diseases."

While Burkholderia bacteria and cystic fibrosis microbiology remain major research foci, my interests are still wide and I am always getting involved in lots of very interesting molecular microbiology projects. In the last few years, we made a very exciting discovery that the Burkholderia bacteria I had studied as pathogens, also make some very potent antibiotics which kill other multidrug resistant bacteria and fungi. Antibiotic discovery has now become a major new research focus for me.

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I carry out a range of teaching from year 1 to final year undergraduate, and the supervision of postgraduate MRes project students. Current teaching includes contributions to:

  • BI1003 Organisms and Environment - An introduction to medically relevant bacteria
  • BI2332 Concepts of Disease - a practical on outbreaks of infection and lectures on meningitis and Human Immunodeficiency Virus
  • BI3155 Infection biology and epidemiology - lectures on cystic fibrosis lung infections and antimicrobial resistance.

Overview

The aim of my group's research is to dissect the natural biology and virulence of opportunistic bacterial pathogens, using molecular and genomic research strategies. Notable findings from these studies are highlighted below.

Advances in cystic fibrosis microbiology

We have focussed on Pseudomonas aeruginosa and Burkholderia cepacia complex bacteria which cause problematic lung infections in people with cystic fibrosis (CF) and more recently started to examine the lung microbiota as follows:

  • P. aeruginosa adapts to a non-motile phenotype during CF lung infection (see Mahenthiralingam et al. 1994).
  • PCR-fingerprinting methods and the molecular epidemiology of CF pathogens P. aeruginosa and B. cepacia complex (see Mahenthiralingam et al. 1996)
  • A DNA marker for transmissible B. cepacia complex bacteria (see Mahenthiralingam et al. 1997)
  • Rapid DNA diagnostics for B. cepacia complex and Burkholderia species identification (see Mahenthiralingam et al. 2000 and Payne et al. 2005).
  • Finding that that B. cenocepacia could replace B. multivorans infection in people with CF (see Mahenthiralingam et al. 2001)
  • Identification of the first B. cenocepacia pathogenicity island (see Baldwin et al. 2004)
  • Collaborative development of a multilocus sequence typing (MLST) scheme for the B. cepacia complex (Baldwin et al. 2005; see http://pubmlst.org/bcc)
  • Linkage of a microbial metagenome to a cultivable, globally distributed Bcc strain (see Mahenthiralingam et al. 2006)
  • Demonstration of clonality between environmental and clinical Burkholderia strains (see Baldwin et al. 2007)
  • Assisting with the taxonomic characterisation of multiple new B. cepacia complex species and the expansion of the MLST scheme to include all Burkholderia species (see Spilker et al. 2009).
  • Rapid microbiota-based diagnostics of CF lung infection for rapid detection of emerging antibiotic resistant pathogens (see Flight et al. 2015)
  • Collaborative microbiota analysis of induced CF sputum (see Ronchetti et al. 2018)

Advances in Burkholderia genomics

We have applied multiple genomic analyses to Burkholderia bacteria as follows:

  • We collaboratively initiated and characterised multiple Burkholderiagenomes, including B. xenovorans genome (see Chain et al. 2006) and first publication of a B. cepacia complex genome for B. cenocepacia J2315 (see Holden et al. 2009).
  • The application of signature tagged transposon mutagenesis to study of B. vietnamiensis in ecological settings (see O'Sullivan et al. 2007)
  • Global gene expression analysis B. cenocepacia during growth in CF sputum (see Drevinek et al. 2008).
  • Stable evolution of antibiotic resistance in B. cenocepacia and mapping of resistance gene pathways (see Sass et al. 2011).
  • The discovery of the low oxygen regulated locus for persistence of B. cenocepacia in the CF lung (see Sass et al. 2013)

 Advances in industrial and applied microbiology

Several projects have been carried out with industrial partners applying our expertise in molecular microbiology to questions in applied microbiology including:

  • With funding from Cultech Ltd. (http://www.cultech.co.uk) we used PCR genotyping to track probiotics after consumption (see Mahenthiralingam et al. 2009) and genomics to understand the population biology of Lactobacillus acidophilus (see Bull et al. 2014).
  • Bacterial contamination of fuels with industrial partner ECHA Microbiology Ltd. (http://www.echamicrobiology.co.uk; see (see White et al. 2011).
  • Bacterial contamination in non-sterile industrial products. We have also been working with Unilever Research and Development (Port Sunlight) and their Safety and Environmental Assurance Centre (SEAC; Colworth) (http://www.unilever.co.uk), examining both B. cepacia complex and P. aeruginosa bacteria as objectionable organisms in industry.
  • We identified that multiple B. cepacian complex species can cause industrial contamination and showed that efflux is a key preservative resistance mechanism (see Rushton et al. 2013).
  • Evaluation of growth media for isolation of P. aeruginosa from industrial products has also been carried out (see Weiser et al. 2014)
  • Mapping the global transcriptomic responses of P. aeruginosa to preservatives (Green et al. 2018)

Burkholderia: Antibiotic discovery and biotechnology

More recently, we have established an antibiotic discovery program exploiting Burkholderia bacteria as a novel source of antibiotics:

  • Mapping the biosynthetic pathway and chemistry of enacyloxin IIa, a potent antibiotic produced by Burkholderia ambifaria (see Mahenthiralingam et al. 2011)
  • Identify that Burkholderia gladioli produces the macrolide antibiotic gladiolin which is highly active of Mycobacteria tuberculosis.

Collaborators

International

  • International Burkholderia cepacia Working Group (IBCWG; https://ibcwg.org)
  • Prof. David Speert and Dr. James Zlosnik, University of British Columbia, Vancouver, Canada
  • Prof. Peter Vandamme and Prof. Tom Coenye, University of Gent, Gent, Belgium
  • Prof. John LiPuma, University of Michigan, Ann Arbor, Michigan USA
  • Prof. Leo Eberl, University of Zurich, Zurich, Switzerland
  • Prof. Miguel Valvano, Centre for Infection and Immunity, Queen's University of Belfast, Belfast
  • Dr. Pavel Drevinek, 2nd Medical School, University of Prague, Prague, Czech Republic

National

  • Andrew Weightman, Julian Marchesi, Tom Connor, Jim Murray, Colin Berry and Hilary Rogers, Cardiff School of Biosciences, and Julian Forton, Cardiff School of Medicine, Cardiff University
  • Gregory Challis, Matthew Jenner and Lijiang Song, Department of Chemistry, University of Warwick, Coventry
  • Julian Parkhill, The Wellcome Trust Sanger Institute, Hinxton, Cambridge
  • Unilever Research and Development (Port Sunlight) and Unilever Safety and Environmental Assurance Centre (SEAC; Colworth)

Grants

  • Biology and Biotechnology Research Council
  • Unilever Research and Development, UK

Current group members

  • Dr. Rebecca Weiser (WeiserRM@cardiff.ac.uk)
  • Dr. Gordon Webster (WebsterG@cardiff.ac.uk)
  • Alex Mullins (MullinsA@cardiff.ac.uk)
  • Edward Cunningham-Oakes (Cunningham-OakesE@cardiff.ac.uk)
  • Amal Alswat (AlswatA@cardiff.ac.uk)
  • Yoana Petrova (PetrovaYD@cardiff.ac.uk)
  • Kasia Parfitt (ParfittKM@cardiff.ac.uk)
  • Nico Bruyniks (BruyniksN@cardiff.ac.uk)

Past group members

  • Dr. Laura Rushton
  • Dr. Angharad Green
  • Dr. Matthew Bull
  • Dr. Andrea Sass
  • Dr. Othman Boaisha
  • Dr. Judith White
  • Dr. Helen Rose
  • Dr. Pavel Drevinek
  • Dr. Louise O'Sullivan
  • Dr. Adam Baldwin
  • Dr. Deborah Lewis
  • Dr. George Payne
  • Dr. Saber Yezli
  • Ms. Angela Marchbank