Prof Matt Holden

Prof Matt Holden

I started my research career with a PhD at Warwick University, studying the distribution and regulation of cryptic antibiotic genes in environmental and plant pathogenic bacteria. As a postdoc I then spent four years at the University of Nottingham, investigating bacterial communication. Initially working on the role of N-acyl homoserine lactones in quorum sensing in Pseudomonads, and then moving ‘languages’ to investigate peptide autoinducer-dependent regulation of virulence in Staphylococcus aureus. I then joined the The Wellcome Trust Sanger Institute in 2000, and have involved in the analysis of the genomes of a wide range of bacterial pathogens including Yersinia pestis, Salmonella typhi, Streptococcus pyogenes, Burkholderia pseudomallei, Burkholderia cenocepacia and S. aureus. With developments in next generation sequencing, the focus of my work has shifted towards populations studies, investigating genome diversity and pathogen evolution, as well as the application of sequencing in clinical microbiology. In 2013 I moved to the Medical School at University St Andrews to establish a research group focusing on experimental and translational pathogen genomics.

My research interest include: the survival and evolution of MRSA, and probing the link between a pathogen’s genotype and virulence, and also the application of genomics in clinical setting to combat hospital-associated infections.

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Research Overview from research@st-andrews

Since the first bacterial genome was sequenced in 1995, whole genome sequencing (WGS) has provided unprecedented insights into the genetics and evolution of microbial pathogens. Having worked at the Sanger Institute 13 years on a broad range of bacterial genomes, I recently moved to the School of Medicine establishing a pathogenomics group. Research in my group is directed at two main areas: translational genomics, the application of WGS in clinical microbiology; and experimental genomics, using data WGS to investigate the relationship between pathogens’ genotypes and phenotypes.

The research areas that the group are focused on include: developing rapid WGS to combat hospital-associated infections, the molecular basis of antibiotic resistance and virulence, and epidemiology and evolution of methicillin resistant S. aureus (MRSA).

source: research@st-andrews
Recent publications listed in research@st-andrews
Bossé, JT, Li, Y, Sárközi, R, Fodor, L, Lacouture, S, Gottschalk, M, Amoribieta, MC, Angen, Ø, Nedbalcova, K, Holden, MTG, Maskell, DJ, Tucker, AW, Wren, BW, Rycroft, AN, Langford, PR & on behalf of the BRaDP1T consortium 2018, 'Proposal of serovars 17 and 18 of Actinobacillus pleuropneumoniae based on serological and genotypic analysis' Veterinary Microbiology, vol In press. DOI: 10.1016/j.vetmic.2018.02.019
Casabona, MG, Kneuper, H, Alferes de Lima, D, Harkins, CP, Zoltner, M, Hjerde, E, Holden, MTG & Palmer, T 2017, 'Haem-iron plays a key role in the regulation of the Ess/type VII secretion system of Staphylococcus aureus RN6390' Microbiology, vol Latest Article. DOI: 10.1099/mic.0.000579
Casabona, MG, Buchanan, G, Zoltner, M, Harkins, CP, Holden, MTG & Palmer, T 2017, 'Functional analysis of the EsaB component of the Staphylococcus aureus Type VII secretion system' Microbiology, vol Latest Article. DOI: 10.1099/mic.0.000580
Harkins, CP, Pettigrew, KA, Oravcova, K, Gardner, J, Hearn, R, Rice, D, Mather, AE, Parkhill, J, Brown, SJ, Proby, CM & Holden, MT 2017, 'The genetic diversity of Staphylococcus aureus colonisation in atopic eczema disease flare' Journal of Investigative Dermatology, vol 137, no. 10, pp. S258-S258.
Sarovich, DS, Chapple, SNJ, Price, EP, Mayo, M, Holden, MTG, Peacock, SJ & Currie, BJ 2017, 'Whole-genome sequencing to investigate a non-clonal melioidosis cluster on a remote Australian island' Microbial Genomics, vol 3, no. 8, e000117. DOI: 10.1099/mgen.0.000117
Hsu, L-Y, Holden, MTG, Koh, TH, Pettigrew, KA, Cao, D, Hon, PY, Sergio, DM, Pena, E & Ogden, BE 2017, 'ST3268: a geographically widespread primate MRSA clone' Journal of Antimicrobial Chemotherapy, vol 72, no. 8, pp. 2401-2403. DOI: 10.1093/jac/dkx120
Björnsdóttir, S, Harris, SR, Svansson, V, Gunnarsson, E, Sigurðardóttir, ÓG, Gammeljord, K, Steward, KF, Newton, JR, Robinson, C, Charbonneau, ARL, Parkhill, J, Holden, MTG & Waller, AS 2017, 'Genomic dissection of an Icelandic epidemic of respiratory disease in horses and associated zoonotic cases' mBio, vol 8, no. 4, e00826-17. DOI: 10.1128/mBio.00826-17
Harkins, CP, Pichon, B, Doumith, M, Parkhill, J, Westh, H, Tomasz, A, de Lencastre, H, Bentley, SD, Kearns, AM & Holden, MTG 2017, 'Methicillin-resistant Staphylococcus aureus emerged long before the introduction of methicillin into clinical practice' Genome Biology, vol 18, 130. DOI: 10.1186/s13059-017-1252-9
Donker, T, Reuter, S, Scriberras, J, Reynolds, R, Brown, NM, Török, ME, James, R, Network, EOEMR, Aanensen, DM, Bentley, SD, Holden, MTG, Parkhill, J, Spratt, BG, Peacock, SJ, Feil, EJ & Grundmann, H 2017, 'Population genetic structuring of methicillin-resistant Staphylococcus aureus clone EMRSA-15 within UK reflects patient referral patterns' Microbial Genomics, vol 3, no. 7, e000113. DOI: 10.1099/mgen.0.000113
Chow, A, Lim, VW, Khan, A, Pettigrew, K, Lye, DCB, Kanagasabai, K, Phua, K, Krishnan, P, Ang, B, Marimuthu, K, Hon, P-Y, Koh, J, Leong, I, Parkhill, J, Hsu, L-Y & Holden, MTG 2017, 'MRSA transmission dynamics among interconnected acute, intermediate-term, and long-term healthcare facilities in Singapore' Clinical Infectious Diseases, vol 64, no. suppl_2, pp. S76-S81. DOI: 10.1093/cid/cix072
Kalimuddin, S, Chen, SL, Lim, CTK, Koh, TH, Tan, TY, Kam, M, Wong, CW, Mehershahi, KS, Chau, ML, Ng, LC, Tang, WY, Badaruddin, H, Teo, J, Apisarnthanarak, A, Suwantarat, N, Ip, M, Holden, MTG, Hsu, LY, Barkham, T & for the Singapore Group B Streptococcus Consortium 2017, '2015 epidemic of severe Streptococcus agalactiae sequence type 283 infections in Singapore associated with the consumption of raw freshwater fish: a detailed analysis of clinical, epidemiological, and bacterial sequencing data' Clinical Infectious Diseases, vol 64, no. suppl_2, pp. S145-S152. DOI: 10.1093/cid/cix021
Bossé, JT, Li, Y, Rogers, J, Crespo, RF, Li, Y, Chaudhuri, RR, Holden, MTG, Maskell, DJ, Tucker, AW, Wren, BW, Rycroft, AN, Langford, PR & BRaDP1T Consortium 2017, 'Whole genome sequencing for surveillance of antimicrobial resistance in Actinobacillus pleuropneumoniae' Frontiers in Microbiology, vol 8, 311. DOI: 10.3389/fmicb.2017.00311
Chewapreecha, C, Holden, MTG, Vehkala, M, Välimäki, N, Yang, Z, Harris, SR, Mather, AE, Tuanyok, A, De Smet, B, Le Hello, S, Bizet, C, Mayo, M, Wuthiekanun, V, Limmathurotsakul, D, Phetsouvanh, R, Spratt, BG, Corander, J, Keim, P, Dougan, G, Dance, DAB, Currie, BJ, Parkhill, J & Peacock, SJ 2017, 'Global and regional dissemination and evolution of Burkholderia pseudomallei' Nature Microbiology, vol 2, 16263. DOI: 10.1038/nmicrobiol.2016.263
Ellington, MJ, Ekelund, O, Aarestrup, FM, Canton, R, Doumith, M, Giske, C, Grundman, H, Hasman, H, Holden, MTG, Hopkins, KL, Iredell, J, Kahlmeter, G, Köser, CU, MacGowan, A, Mevius, D, Mulvey, M, Naas, T, Peto, T, Rolain, J-M, Samuelsen, Ø & Woodford, N 2017, 'The role of whole genome sequencing in antimicrobial susceptibility testing of bacteria: report from the EUCAST Subcommittee' Clinical Microbiology and Infection, vol 23, no. 1, pp. 2-22. DOI: 10.1016/j.cmi.2016.11.012
Afshar, B, Turner, CE, Lamagni, T, Smith, K, Al-Shahib, A, Underwood, A, Holden, MTG, Efstratiou, A & Sriskandan, S 2017, 'Enhanced nasopharyngeal infection and shedding associated with an epidemic lineage of emm3 group A Streptococcus' Virulence, vol 8, no. 7, pp. 1390-1400. DOI: 10.1080/21505594.2017.1325070
Argimón, S, Abudahab, K, Goater, RJE, Fedosejev, A, Bhai, J, Glasner, C, Feil, EJ, Holden, MTG, Yeats, CA, Grundmann, H, Spratt, BG & Aanensen, DM 2016, 'Microreact: visualizing and sharing data for genomic epidemiology and phylogeography' Microbial Genomics, vol 2, no. 11. DOI: 10.1099/mgen.0.000093
Chapple, SNJ, Sarovich, DS, Holden, MTG, Peacock, SJ, Buller, N, Golledge, C, Currie, BJ, Mayo, M & Price, EP 2016, 'Whole-genome sequencing of a quarter-century melioidosis outbreak in temperate Australia uncovers a region of low-prevalence endemicity' Microbial Genomics, vol 2, no. 7. DOI: 10.1099/mgen.0.000067
Bosse, JT, Li, Y, Crespo, RF, Chaudhuri, RR, Rogers, J, Holden, MTG, Maskell, DJ, Tucker, AW, Wren, BW, Rycroft, AN, Langford, PR & BRaDP1T Consortium 2016, 'ICEApl1, an integrative conjugative element related to ICEHin1056, identified in the pig pathogen Actinobacillus pleuropneumoniae' Frontiers in Microbiology, vol 7, 810. DOI: 10.3389/fmicb.2016.00810
Jamrozy, DM, Harris, SR, Mohamed, N, Peacock, SJ, Tan, CY, Parkhill, J, Anderson, AS & Holden, MTG 2016, 'Pan-genomic perspective on the evolution of the Staphylococcus aureus USA300 epidemic' Microbial Genomics, vol 2, no. 5, pp. 1-14. DOI: 10.1099/mgen.0.000058