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Eshwar Mahenthiralingam  BSc PhD FHEA

Yr Athro Eshwar Mahenthiralingam

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BSc PhD FHEA

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Timau a rolau for Eshwar Mahenthiralingam

  • Pennaeth yr Ysgol, Ysgol y Biowyddorau

    Ysgol y Biowyddorau

Trosolwyg

Trosolwg o'r ymchwil

Mae fy ngrŵp wedi astudio pathogenesis, biotechnoleg a rhyngweithiadau ecolegol pathogenau oportunistaidd bacteriol, ac ar hyn o bryd mae'n cwmpasu tair thema ryngddisgyblaethol:

  • Dadansoddiadau microbiota ffibrosis systig a microbiota heintiau yr ysgyfaint
  • Genomeg Burkholderia a chynhyrchu metabolit arbenigol
  • Microbioleg ddiwydiannol ac ymwrthedd gwrthficrobaidd

Microbiomau, Microbau a Gwybodeg

Mae'r labordy Mahenthiralingam yn rhan o'r grŵp Microbiomau, Microbau a Gwybodeg (MMI) sydd ar hyn o bryd yn cynnwys timau ymchwil Helen Brown, Cedric Berger, Thomas Connor, Arthur Morris, Katherine Smith, Andrew Weightman a Catrin Wlliams. Rydym hefyd yn gweithio o fewn yr Is-adran Organebau a'r Amgylchedd.

 

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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 ([email protected])

Dr. Gordon Webster ([email protected])

Dr. Alex Mullins ([email protected])

Dr. Laura Rushton ([email protected])

Mr. Abdullah Aseeri ([email protected])

Ms. Kasia Parfitt ([email protected])

Ms. Yoana Petrova ([email protected])

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

Rwy'n cynnal ystod o addysgu o Flwyddyn 1 (lefel 4) i Flwyddyn Olaf (lefel  6) israddedig, gan gynnwys goruchwylio myfyrwyr prosiect israddedig blwyddyn olaf a phrosiect Meistr Integredig (lefel 7).

Mae'r addysgu presennol yn cynnwys cyfraniadau at:

BI1003 Organebau a'r Amgylchedd - Cyflwyniad i facteria sy'n berthnasol yn feddygol

BI2332 Cysyniadau Clefyd - Darlith ac ymarferion ar achosion o haint bacteriol.

BI2132 Geneteg a'i Gymwysiadau - Cysyniadau ac enghreifftiau mewn esblygiad bacteriol a geneteg.

 

Prosiectau Ymchwil Blwyddyn Olaf a Myfyrwyr Meistr Integredig - Rwy'n hapus i ddatblygu a chynnal prosiectau ymchwil ar gyfer myfyrwyr israddedig yn seiliedig ar fy meysydd ymchwil cyfredol (gweler Ymchwil) a gallaf deilwra'r rhain ar gyfer myfyrwyr biofeddygol, biolegol, biocemegol neu geneteg oherwydd natur ryngddisgyblaethol fy arbenigedd.

Bywgraffiad

 

Trosolwg

Ar hyn o bryd rwy'n arwain Ysgol y Biowyddorau ym Mhrifysgol Caerdydd ac yn arbenigo mewn microbioleg foleciwlaidd, gyda ffocws penodol ar pathogenau microbaidd sy'n effeithio ar bobl â ffibrosis systig (CF). Mae fy ymchwil wedi helpu i lunio dealltwriaeth fyd-eang o Pseudomonas aeruginosa a'r cymhleth Burkholderia cepacia, gan ddatgelu sut mae'r bacteria hyn yn addasu, lledaenu ac esblygu mewn lleoliadau clinigol ac amgylcheddol.

Taith Academaidd

Dechreuais fy nhaith academaidd yng Nghaerdydd, gan ennill gradd Anrhydedd Dosbarth Cyntaf mewn Bioleg Gymhwysol, ac yna PhD mewn Geneteg Mycobacteriol yn y Sefydliad Cenedlaethol ar gyfer Ymchwil Feddygol yn Llundain. Dros y blynyddoedd, rwyf wedi dal sawl rôl arweinyddiaeth, gan gynnwys Cyd-Gyfarwyddwr Ymchwil ar gyfer yr Ysgol Biowyddoniaeth, ac REF2021 Arweinydd Uned ar gyfer y Gwyddorau Biolegol ym Mhrifysgol Caerdydd. Yn allanol, rwyf wedi gweithio gyda'r Cyngor Ymchwil Biotechnoleg a Gwyddorau Biolegol (BBSRC) fel adolygydd panel grant ac yna'n Ddirprwy Gadeirydd Panel B (Planhigion, microbau, bwyd a chynaliadwyedd) tan fis Ebrill 2025.

Ymchwil

Mae fy ymchwil wedi cyfrannu at ddatblygu diagnosteg DNA cyflym, olrhain epidemiolegol byd-eang, ac offer teipio moleciwlaidd ar gyfer pathogenau CF bacteriol. Mae'r datblygiadau hyn wedi cefnogi dosbarthu rhywogaethau bacteriol newydd ac adnabod ynysoedd pathogenedd newydd. Dros y blynyddoedd mae hyn hefyd wedi ehangu i ymchwil biotechnolegol i ddarganfod gwrthfiotigau newydd, datblygu dulliau ar gyfer bioreoli pathogenau cnydau, ac atal halogiad microbaidd mewn diwydiant.

Mentora a Hyfforddiant

O fewn y byd academaidd, rwyf wedi hyfforddi nifer o fyfyrwyr PhD ac wedi archwilio traethodau ôl-raddedig yn genedlaethol ac yn rhyngwladol. Rwyf wedi gwasanaethu fel arholwr allanol ar gyfer rhaglenni MSc ac yn parhau i arwain a mentora gwyddonwyr ar ddechrau gyrfa.  Hyrwyddo microbioleg a genomeg, a datrys problemau sy'n gysylltiedig â microbau yw'r hyn sy'n fy nghyffroi, ac mae'n wych cefnogi'r genhedlaeth nesaf o ymchwilwyr sy'n hyfforddi yn y meysydd hyn.

Anrhydeddau a dyfarniadau

  • Cymrodoriaeth yr Academi Addysg Uwch (FHEA; Mai 2023)
  • Diploma Lefel 5 mewn Rheolaeth Brifysgol Ymarferol (Mehefin 2015)
  • Cadair mewn Microbioleg Moleciwlaidd (Prifysgol Caerdydd, Awst 2011)
  • Gwobr y Llywyddion, Gwobr teithio ymchwil y Gymdeithas Microbioleg Gymhwysol (Awst 2008)
  • Gwobr deithio ymchwilydd cyfnod cynnar Prifysgol Caerdydd (Awst 2006; ymchwilydd gwadd ym Mhrifysgol Harvard a'r Broad Institute, Sefydliad Technoleg Masschusetts, Boston, UDA)
  • Gwobr Datblygu Gyrfa; Cymdeithas Ysgyfaint British Columbia (2 flynedd o Hydref 1997)
  • Ysgoloriaeth Ymchwil, Cyngor Ymchwil Feddygol Canada (5 mlynedd, o 1999 ymlaen; gwrthododd ddechrau swydd barhaol ym Mhrifysgol Caerdydd)
  • Cymrodoriaeth, Cymdeithas Ysgyfaint British Columbia; Sefydliad Ymchwil BC ar gyfer Iechyd Plant a Theuluoedd (1 flwyddyn o Orffennaf 1997)
  • Cymrodoriaeth Ymchwil Ôl-ddoethurol; Sefydliad Ffibrosis Systig Canada (3 blynedd; o fis Ionawr 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, tymor 8 mlynedd fel aelod llawn o'r bwrdd golygyddol
  • Panel B BBSRC Planhigion, microbau, bwyd a chynaliadwyedd: aelod o'r gronfa (Ionawr 2017 i Hydref 2018); aelod craidd (Tachwedd 2018 i Ionawr 2022), a Dirprwy Gadeirydd (Chwefror 2022 i Ebrill 2025)
  • Adolygydd gwadd: Sefydliad Ffibrosis Systig yr Unol Daleithiau, Pwyllgor Ymchwil a Hyfforddiant Mawrth 2009 ymlaen; Ffibrosis Systig Canada, aelod o'r Panel Adolygu Ymchwil, 2005 ymlaen; Cyngor Ymchwil Hong Kong, panel adolygu grantiau allanol o 2012 ymlaen. Adolygiadau gwahoddedig ar gyfer: Ymddiriedolaeth Ffibrosis Systig, Sefydliadau Ymchwil Iechyd Canada, Ymddiriedolaeth Wellcome, MRC, a NERC

Meysydd goruchwyliaeth

Mae gen i ddiddordeb mewn goruchwylio myfyrwyr ôl-raddedig sydd â diddordeb yn y meysydd prosiect canlynol:

  • Microbioleg Moleciwlaidd
  • Genomeg, pathogenesis ac ecoleg clefydau heintus bacteriol
  • Micro-organebau sy'n cynhyrchu gwrthfiotigau a darganfod metabolit arbenigol
  • Deall a brwydro yn erbyn ymwrthedd gwrthficrobaidd mewn bacteria
  • Nodweddu heintiau ffibrosis systig yr ysgyfaint, bacteria Pseudomonas aeruginosa a Burkholderia
  • Dadansoddiad cymunedol microbaidd mewn clefydau heintus a'r amgylchedd naturiol

 

Goruchwyliaeth gyfredol

Owen Griffiths

Owen Griffiths

Ymchwilydd PhD

Brooklyn Rowlands

Brooklyn Rowlands

Ymgysylltu

Array

News articles

Gallai bacteria o gleifion ffibrosis systig frwydro yn erbyn TB sy'n gwrthsefyll gwrthfiotigau.

Trin TB sy’n gallu gwrthsefyll gwrthfiotigau

23 June 2017

Gallai bacteria o gleifion ffibrosis systig frwydro yn erbyn TB sy'n gwrthsefyll gwrthfiotigau.

Prifysgol Caerdydd yn arddangos ei gwaith mewn digwyddiad gwyddoniaeth a thechnoleg blynyddol

Gwyddoniaeth a'r Cynulliad

07 June 2017

Prifysgol Caerdydd yn arddangos ei gwaith mewn digwyddiad gwyddoniaeth a thechnoleg blynyddol

Contact Details

Email [email protected]
Telephone +44 29208 75875
Campuses Adeilad Syr Martin Evans, Llawr Trydydd, Ystafell Dwyrain 3.32, Rhodfa'r Amgueddfa, Caerdydd, CF10 3AX

Arbenigeddau

  • Rheoli Heintiau
  • ymwrthedd gwrthficrobaidd
  • Biotechnoleg amaethyddol