Ewch i’r prif gynnwys
Eshwar Mahenthiralingam

Yr Athro Eshwar Mahenthiralingam

Professor

Ysgol y Biowyddorau

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Research overview

My group has studied the pathogenesis, biotechnology and ecological interactions of bacterial opportunistic pathogens. Current research within the group splits across three interdisciplinary themes:

  • Cystic fibrosis microbiology and lung infection microbiota analyses
  • Burkholderia genomics and specialised metabolite production
  • Industrial microbiology and antimicrobial resistance

Microbiomes, Microbes and Informatics

The Mahenthiralingam lab is part of the Microbiomes, Microbes and Informatics (MMI) group that currently comprises the research teams of Cedric Berger, Thomas Connor, Katherine Smith and Andrew Weightman. We also work closely with the Cardiff Research into Infection and Parasites in Ecological Systems (CRIPES) within the Organisms and Environment Division. Collectively, we have over 50 active research staff and postgraduate students, and we welcome approaches by potential fellowship applicants and funded PhD students to expand our strategic research on Microbiomes, Microbes and Informatics.

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Articles

Ymchwil

Cystic fibrosis (CF) microbiology and lung infection microbiota analyses

We are examining the pathogenesis, antimicrobial resistance, microbiota interactions and genomics of Pseudomonas aeruginosa and Burkholderia bacteria, which cause problematic lung infections in people with cystic fibrosis. My early career expertise and studies are outlined under the bibliography section; current projects are described below

Microbiota analysis of CF lung infections

We successfully applied a simple bacterial microbiota-profiling PCR to CF sputum samples and showed it could rapidly detect emerging antibiotic resistant pathogens such as Burkholderia, Achromobacter and Stenotrophomonas (see Flight et al. 2015). In collaboration with Julian Forton, we found that the microbiota of induced sputum (a safe sampling method for children with CF who do not produce sputum) contained bacterial diversity that was representative of their lung infections and overlapped sampling by bronchoalveolar lavage (the gold standard but invasive sampling procedure) (see Ronchetti et al. 2018). We have also worked with AlgiPharma AS to track microbiota changes in the CF lung during their clinical trial of Oligo G, a novel anti-infective therapeutic (see Weiser et al. 2021).

Phylogenomics of Pseudomonas aeruginosa and Burkholderia bacteria

We have been involved in collaborative studies to define and evaluate panels of representative P. aeruginosa strains (Cullen et al. 2015) and recently mapped the phylogenomics of this species (Weiser and Green et al. 2019). Our genomic characterisation of Burkholderia has been extensive, recently releasing a dataset of 450 genomes (Mullins et al. 2020) and characterising them in a number of studies (see below).

Burkholderia genomics and specialised metabolite production

We have undertaken studies examining the pathogenomics of Burkholderia bacteria. Highlights include:

Pathogenomics of Burkholderia in CF

We published the first complete genome for the Burkholderia cenocepacia strain J2315 (Holden et al. 2009). We also undertook the first global gene expression analyses B. cenocepacia grown CF sputum (see Drevinek et al. 2008). Using a B. cenocepacia microarray, we mapped the evolution of antibiotic resistance in B. cenocepacia (Sass et al. 2011), and subsequently discovered the low oxygen regulated locus which enables persistence of this pathogen in the oxygen-deprived CF lung (Sass et al. 2013).

Genome mining Burkholderia for specialised metabolites and novel antibiotics

In 2007, we began screening our large collection of Burkholderia bacteria for the production of novel antibiotics. This led to the discovery of the polyketide antibiotic enacyloxin IIa and its unique biosynthetic pathway in Burkholderia ambifaria (Mahenthiralingam et al. 2011). Since 2014, we have led a successful BBSRC-funded interdisciplinary collaboration with Prof Greg Challis (University of Warwick), to characterise novel specialized metabolites produced by Burkholderia bacteria. After characterising enacyloxin, our interdisciplinary teams have followed up with discoveries of:

  • Gladiolin, a novel macrolide capable of killing Mycobacterium tuberculosis (Song et al. 2017)
  • Cepacin, a potent polyyne antibiotic and core component of the biopesticidal ability of Burkholderia to protect crops plants against pathogen attack (Mullins et al. 2019). The discovery of the biopesticidal activity of cepacin resulted from interdisciplinary collaborations with Prof. Jim Murray and his plant research group.
  • Iscosalides produced by Burkholderia gladioli (Jenner et al. 2019)
  • Unique enacyloxin biosynthesis mechanisms that open up possibilities for molecular engineering of this potent antibiotic (Masschelein et al. 2019)
  • Novel bolagladin lipodepsipeptide metabolites produced by Burkholderia gladioli that can bind iron (Dashti et al. 2020)
  • The novel Burkholderia glutarimide antibiotic, gladiostatin, with anticancer activity (Nakou et al. 2020).
  • The enormous potential within a collection of 450 genomes we have released to aid specialized metabolite discovery in Burkholderia bacteria (Mullins et al. 2020)
  • The diversity of potentially beneficial and toxic specialized metabolites encoded and expressed by the CF pathogen, Burkholderia gladioli (Jones et al. 2021)

Industrial microbiology and antimicrobial resistance

Pseudomonas and Burkholderia bacteria have high intrinsic antimicrobial resistance and can occasionally overcome preservative formulations, causing contamination in a range of non-sterile industrial products. We have worked with a number of commercial sponsors to understand industrial microbiology problems as follows.

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) examining both Burkholderia and Pseudomonas bacteria as objectionable contaminant micro-organisms that occur in industry. We showed that multiple B. cepacia complex species can cause industrial contamination and use efflux as a key preservative resistance mechanism (see Rushton et al. 2013). We mapped the global transcriptomic responses of P. aeruginosa to preservatives (Green et al. 2018) and showed for the first time that strains from industry have the largest genomes and megaplasmids found in this antibiotic resistant species (Weiser and Green et al. 2019). Using molecular approaches we have also shown that ethylzingerone is a highly effective preservative that kills Burkholderia bacteria by novel mechanisms (Ruston et al. 2020).

Improving the reporting and identification of antimicrobial resistant industrial contaminants

Current guidelines used in the manufacture of non-sterile product do not necessarily require reporting or complete identification of bacteria which overcome preservation and cause contamination. We have shown that nearly 50% industrial product recall reports within Europe do not identify the causative organism, yet when contaminants are identified they constitute antibiotic resistant bacteria such as Pseudomonas, Burkholderia and Enterobacteriaceae (Cunningham-Oakes et al. 2019). We are now using genomic taxonomy methods to accurately identify industrial contaminants (Cunningham-Oakes et al. 2020).

Current Collaborators

International

International Burkholderia cepacia Working Group (IBCWG)

Prof. Peter Vandamme and Prof. Tom Coenye, University of Gent, Gent, Belgium

Prof. John LiPuma, University of Michigan, Ann Arbor, Michigan USA

National

Andrew Weightman, Tom Connor, Cedric Berger, Julian Marchesi (now at Imperial) and Jim Murray, Cardiff School of Biosciences, and Julian Forton, Cardiff School of Medicine, Cardiff University

Gregory Challis, Jinlian Zhao and Matthew Jenner, Department of Chemistry, University of Warwick, Coventry

Julian Parkhill, The Wellcome Trust Sanger Institute, Hinxton, Cambridge

Andy Bailey, University of Bristol

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

The US Cystic Fibrosis Foundation

The Sêr Cymru II Welsh Government Fellowship Scheme

Current group members

Dr. Rebecca Weiser (WeiserRM@cardiff.ac.uk)

Dr. Gordon Webster (WebsterG@cardiff.ac.uk)

Dr. Alex Mullins (MullinsA@cardiff.ac.uk)

Dr. Laura Rushton (RushtonL3@cardiff.ac.uk)

Mr. Abdullah Aseeri (AseeriAA@cardiff.ac.uk)

Ms. Kasia Parfitt (ParfittKM@cardiff.ac.uk)

Ms. Yoana Petrova (PetrovaYD@cardiff.ac.uk)

Past postgraduate trainees

PhD. Dr. Edward Cunningham-Oakes,  Dr. Amal Alswat, Dr. Angharad Green, Dr. Matthew Bull, Dr. Othman Boaisha, Dr. Judith White, Dr. Helen Rose, Dr. George Payne, Dr. Saber Yezli, and Dr. Brian Jones.

Masters. Ms. Laura Evans, Ms. Fiona Lugg, Mr. Christopher Paisey, Ms. Alice Collins and Mr. Nico Bruyniks.

Past group members

Dr. Andrea Sass, Dr. Pavel Drevinek, Dr. Louise O'Sullivan, Dr. Adam Baldwin, Dr. Deborah Lewis, and Ms. Angela Marchbank

Addysgu

I carry out a range of teaching from year 1 to Final Year undergraduate, including the supervision of final year undergraduate and Integrated Masters project students.

Current teaching includes contributions to:

BI1003 Organisms and Environment - An introduction to medically relevant bacteria

BI2332 Concepts of Disease - Practicals on outbreaks of infection and lectures on  Human Immunodeficiency Virus

BI2132 Genetics and its Applications - Concepts and examples in bacterial evolution and genetics.

BI3155 Infection Biology and Epidemiology - lectures on antimicrobial resistance, cystic fibrosis lung infections and meningcoccal meningitis

Year 2 Week Long Practicals - I developed and lead a week long practical on antibiotic resistance and antibiotic discovery. This allows students to understand the dilemmas of antimicrobial resistance and drug development, and also isolate and characterise antibiotic producing bacteria from the natural enviroment

Final Year Research Projects and Integrated Masters Students - I am happy to develop and host research projects for undergraduate students based on my current research areas (see Research) and can tailor these for biomedical, biological, biochemical or genetics students because of the interdisciplinary nature of my expertise.

Bywgraffiad

Current position

Co-Director of Research and Executive Management Team, Cardiff School of Biosciences

Professor of Molecular Microbiology, Microbiomes, Microbes and Informatics Group, Organisms & Environment Division, Cardiff School of Biosciences, Cardiff University

Education

  • Ph.D. Mycobacterial Genetics; March 1991; Council for National Academic Awards, and Medical Research Council, UK, Mycobacterial Research Laboratory, National Institute for Medical Research,  Mill Hill, London,  UK
  • B.Sc. Applied Biology, First Class Honours, June 1987; University of Wales Institute of Science and Technology (now Cardiff University), Department of Applied Biology, Cardiff, Wales, United Kingdom

Professional experience

  • Co-director of Research and School Executive Management Team (2015 onwards)
  • Cardiff University REF2021 Biological Sciences Unit of Assessment Lead
  • Practical Leadership for University Management & Institute of Leadership and Management Diploma Level 5
  • MSc External Examiner. MSc in Biomedical and Molecular Sciences, University College London (2012 to 2016)
  • PhD examiner. 27 performed to end 2020.

Early career research: cystic fibrosis microbiology 

Pseudomonas aeruginosa in CF. My early postdoctoral research in Vancouver, British Columbia, Canada, showed P. aeruginosa adapts to a non-motile phenotype during CF lung infection to escape capture by lung macrophages (see Mahenthiralingam et al. 1994) and tracked the molecular epidemiology of this major CF pathogen using PCR-genotyping methods (see Mahenthiralingam et al. 1996)

Advancing our early understanding of Burkholderia cepacia complex in CF. In parallel to the postdoctoral research on Pseudomonas, I was able to track the intercontinental spread Burkholderia bacteria within CF populations (Mahenthiralingam et al. 1996), identify a DNA marker for transmissible Burkholderia (see Mahenthiralingam et al. 1997), and pioneer rapid DNA diagnostics for Burkholderia species identification (see Mahenthiralingam et al. 2000; subsequently Payne et al. 2005), and ultimately find that that Burkholderia cenocepacia could replace Burkholderia multivorans infection in people with CF (see Mahenthiralingam et al. 2001). We followed this research up in Cardiff and successfully identified the first B. cenocepacia pathogenicity island (see Baldwin et al. 2004).

Multilocus sequence typing and global epidemiology of Burkholderia. We collaboratively developed a multilocus sequence typing (MLST) scheme for the B. cepacia complex (Baldwin et al. 2005; see http://pubmlst.org/bcc), and use these tools to link a microbial metagenome to a cultivable, globally distributed Bcc strain (see Mahenthiralingam et al. 2006), demonstrate clonality between environmental and clinical Burkholderia strains (see Baldwin et al. 2007), and assist with the taxonomic characterisation of multiple new B. cepacia complex species.

Anrhydeddau a dyfarniadau

  • Presidents Award, Society for Applied Microbiology research travel award (August 2008)
  • Early stage researcher 2006 travel award, Cardiff University, one month visit (August 2006) to collaborate with Prof. Stephen Lory, Harvard University, and the Broad Institute, Masschusetts Institute of Technology, Boston, USA.
  • Career Development Award; British Columbia Lung Association (2 years from October 1997)
  • Research Scholarship, Medical Research Council of Canada (5 years, from 1999 onwards; declined to start permanent position at Cardiff University)
  • Research Associate Fellowship; BC Research Institute for Child and Family Health (1 year from July 1997)
  • Postdoctoral Research Fellowship; Canadian Cystic Fibrosis Foundation (3 years; from January 1991)

Aelodaethau proffesiynol

  • European Cystic Fibrosis Society (2009 onwards). Member of Annual Conference Microbiology Assembly Planning Group (leader for Microbiology 2013 to 2015) and invited serve on the annual conference steering committee from 2016 to 2019.
  • Microbiology Society (1999 onwards)
  • Society for Applied Microbiology (1999 onwards)
  • American Society for Microbiology (1990 onwards)

Safleoedd academaidd blaenorol

  • Reader (2007- August 2011), Cardiff School of Biosciences, Cardiff University
  • Senior Lecturer (2003-2007; address as above)
  • Lecturer Grade (1999-2003; address as above)
  • Assistant Professor (1997-1999), Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada
  • Research Associate (1995-1997; address as above)
  • Canadian CF Foundation Postdoctoral Research Fellow (1991-1995; address as above)

Pwyllgorau ac adolygu

  • 2000-2008 Journal of Clinical Microbiology, 8 year term as a full editorial board member
  • Pool member BBSRC Panel B Plants, microbes, food and sustainability, January 2017 onwards (term to 2023).
  • Core member BBSRC Panel B Plants, microbes, food and sustainability, November 2018 onwards.
  • Guest reviewer: US Cystic Fibrosis Foundation, Research and Research Training Committee March 2009 onwards; Cystic Fibrosis Canada, Research Review Panel member, 2005 onwards; Hong Kong Research Council, external grant review panel from 2012 onwards. Invited reviews for: Cystic Fibrosis Trust, Canadian Institutes of Health Research, The Wellcome Trust, MRC, and NERC

Meysydd goruchwyliaeth

I am interested in supervising students in:

  • Molecular microbiology
  • Genomics, pathogenesis and ecology of bacterial infectious diseases
  • Antibiotic producing microorganisms and specialised metabolite discovery
  • Understanding and combatting antimicrobial resistance in bacteria
  • Characterising cystic fibrosis lung infections, Pseudomonas aeruginosa and Burkholderia bacteria
  • Microbial community analysis in infectious disease and the natural environment

Ymgysylltu

Array

Contact Details

Email MahenthiralingamE@caerdydd.ac.uk
Telephone +44 29208 75875
Campuses Adeilad Syr Martin Evans, Ystafell West 2.06, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX
Ysgol y Biowyddorau yn ennill canlyniadau rhagorol yn FfRhY 2021

Ysgol y Biowyddorau yn ennill canlyniadau rhagorol yn FfRhY 2021

11 May 2022

Gallai dealltwriaeth newydd o wrthfiotig helpu i fynd i’r afael â phathogen sy’n ymwrthol i gyffuriau

Gallai dealltwriaeth newydd o wrthfiotig helpu i fynd i’r afael â phathogen sy’n ymwrthol i gyffuriau

31 October 2019

Manteisio ar facteria llesol er mwyn sicrhau dyfodol cynaliadwy

Manteisio ar facteria llesol er mwyn sicrhau dyfodol cynaliadwy

04 March 2019

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