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
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
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
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 Latest Articles. DOI: 10.1080/21505594.2017.1325070
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
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
Aanensen, DM, Feil, EJ, Holden, MTG, Dordel, J, Yeats, CA, Fedosejev, A, Goater, R, Castillo-Ramírez, S, Corander, J, Colijn, C, Chlebowicz, MA, Schouls, L, Heck, M, Pluister, G, Ruimy, R, Kahlmeter, G, Åhman, J, Matuschek, E, Friedrich, AW, Parkhill, J, Bentley, SD, Spratt, BG, Grundmann, H & European Staphylococcal Reference Laboratory Working Group 2016, 'Whole-genome sequencing for routine pathogen surveillance in public health: a population snapshot of invasive Staphylococcus aureus in Europe' mBio, vol 7, no. 3, e00444-16, pp. 1-15. DOI: 10.1128/mBio.00444-16
Warne, B, Harkins, CP, Harris, SR, Vatsiou, A, Stanley-Wall, N, Parkhill, J, Peacock, SJ, Palmer, T & Holden, MTG 2016, 'The Ess/Type VII secretion system of Staphylococcus aureus shows unexpected genetic diversity' BMC Genomics, vol 17, no. 1, pp. 222. DOI: 10.1186/s12864-016-2426-7
Reuter, S, Török, EM, Holden, MT, Reynolds, R, Raven, KE, Blane, B, Donker, T, Bentley, SD, Aanensen, DM, Grundmann, H, Feil, EJ, Spratt, BG, Parkhill, J & Peacock, SJ 2016, 'Building a genomic framework for prospective MRSA surveillance in the United Kingdom and the Republic of Ireland' Genome Research, vol 26, no. 2, pp. 263-270. DOI: 10.1101/gr.196709.115
Bossé, JT, Chaudhuri, RR, Li, Y, Leanse, LG, Fernandez Crespo, R, Coupland, P, Holden, MTG, Bazzolli, DM, Maskell, DJ, Tucker, AW, Wren, BW, Rycroft, AN, Langford, PR & on behalf of the BRaDP1T consortium 2016, 'Complete genome sequence of MIDG2331, a genetically tractable serovar 8 clinical isolate of Actinobacillus pleuropneumoniae' Genome Announcements, vol 4, no. 1, e01667-15. DOI: 10.1128/genomeA.01667-15
Ba, X, Harrison, EM, Lovering, AL, Gleadall, N, Zadoks, R, Parkhill, J, Peacock, SJ, Holden, MTG, Paterson, GK & Holmes, MA 2015, 'Old drugs to treat resistant bugs: methicillin-resistant Staphylococcus aureus isolates with mecC are susceptible to a combination of penicillin and clavulanic acid' Antimicrobial Agents and Chemotherapy, vol 59, no. 12, pp. 7396-7404. DOI: 10.1128/AAC.01469-15
Laabei, M, Uhlemann, A-C, Lowy, FD, Austin, ED, Yokoyama, M, Ouadi, K, Feil, E, Thorpe, HA, Williams, B, Perkins, M, Peacock, SJ, Clarke, SR, Dordel, J, Holden, M, Votintseva, AA, Bowden, R, Crook, DW, Young, BC, Wilson, DJ, Recker, M & Massey, RC 2015, 'Evolutionary trade-offs underlie the multi-faceted virulence of Staphylococcus aureus' PLoS Biology, vol 13, no. 9, e1002229. DOI: 10.1371/journal.pbio.1002229