Matthew T. G. Holden

ORCID: 0000-0002-4958-2166
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About
Contact & Profiles
Research Areas
  • Antimicrobial Resistance in Staphylococcus
  • Bacterial Identification and Susceptibility Testing
  • Streptococcal Infections and Treatments
  • Bacterial biofilms and quorum sensing
  • Microbial infections and disease research
  • Genomics and Phylogenetic Studies
  • Antibiotic Resistance in Bacteria
  • Bacteriophages and microbial interactions
  • SARS-CoV-2 and COVID-19 Research
  • Bacterial Genetics and Biotechnology
  • Antibiotic Use and Resistance
  • COVID-19 Clinical Research Studies
  • Neonatal and Maternal Infections
  • Urinary Tract Infections Management
  • Plant Pathogenic Bacteria Studies
  • Burkholderia infections and melioidosis
  • Infective Endocarditis Diagnosis and Management
  • Vibrio bacteria research studies
  • Global Maternal and Child Health
  • Laser Design and Applications
  • SARS-CoV-2 detection and testing
  • Animal Virus Infections Studies
  • Atomic and Molecular Physics
  • Mycobacterium research and diagnosis
  • Biochemical and Structural Characterization

University of St Andrews
2016-2025

Public Health Scotland
2020-2024

Catholic University of Health and Allied Sciences
2023

Imperial College London
2022

Quadram Institute
2022

Wellcome Sanger Institute
2012-2021

Exosome Diagnostics (United States)
2021

Public Health England
2021

R&D Systems (United States)
2021

Faculty of Public Health
2021

Abstract Summary: A typical prokaryote population sequencing study can now consist of hundreds or thousands isolates. Interrogating these datasets provide detailed insights into the genetic structure prokaryotic genomes. We introduce Roary, a tool that rapidly builds large-scale pan genomes, identifying core and accessory genes. Roary makes construction genome samples possible on standard desktop without compromising accuracy results. Using single CPU produce consisting 1000 isolates in 4.5...

10.1093/bioinformatics/btv421 article EN cc-by Bioinformatics 2015-07-20

The Gram-negative bacterium Yersinia pestis is the causative agent of systemic invasive infectious disease classically referred to as plague, and has been responsible for three human pandemics: Justinian plague (sixth eighth centuries), Black Death (fourteenth nineteenth centuries) modern (nineteenth century present day). recent identification strains resistant multiple drugs potential use Y. an biological warfare mean that still poses a threat health. Here we report complete genome sequence...

10.1038/35097083 article EN cc-by-nc-sa Nature 2001-10-01

Current methods for differentiating isolates of predominant lineages pathogenic bacteria often do not provide sufficient resolution to define precise relationships. Here, we describe a high-throughput genomics approach that provides high-resolution view the epidemiology and microevolution dominant strain methicillin-resistant Staphylococcus aureus (MRSA). This reveals global geographic structure within lineage, its intercontinental transmission through four decades, potential trace...

10.1126/science.1182395 article EN Science 2010-01-21

Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent drug-resistant strains, presenting a major constantly changing clinical challenge. We sequenced approximately 2.8-Mbp genomes two disease-causing S. strains isolated from distinct settings: recent hospital-acquired representative epidemic methicillin-resistant EMRSA-16 clone (MRSA252), clinically globally prevalent lineage; invasive...

10.1073/pnas.0402521101 article EN Proceedings of the National Academy of Sciences 2004-06-22

Burkholderia pseudomallei is a recognized biothreat agent and the causative of melioidosis. This Gram-negative bacterium exists as soil saprophyte in melioidosis-endemic areas world accounts for 20% community-acquired septicaemias northeastern Thailand where half those affected die. Here we report complete genome B. pseudomallei, which composed two chromosomes 4.07 megabase pairs 3.17 pairs, showing significant functional partitioning genes between them. The large chromosome encodes many...

10.1073/pnas.0403302101 article EN Proceedings of the National Academy of Sciences 2004-09-17

Visualization is frequently used to aid our interpretation of complex datasets. Within microbial genomics, visualizing the relationships between multiple genomes as a tree provides framework onto which associated data (geographical, temporal, phenotypic and epidemiological) are added generate hypotheses explore dynamics system under investigation. Selected static images then within publications highlight key findings wider audience. However, these very inadequate way exploring interpreting...

10.1099/mgen.0.000093 article EN cc-by Microbial Genomics 2016-11-30

Isolates of methicillin-resistant Staphylococcus aureus (MRSA) belonging to a single lineage are often indistinguishable by means current typing techniques. Whole-genome sequencing may provide improved resolution define transmission pathways and characterize outbreaks.

10.1056/nejmoa1109910 article EN New England Journal of Medicine 2012-06-14

The emergence of meticillin-resistant Staphylococcus aureus (MRSA) that can persist in the community and replace existing hospital-adapted lineages MRSA means it is necessary to understand transmission dynamics terms hospitals as one entity. We assessed use whole-genome sequencing enhance detection between these settings.We studied a putative outbreak on special care baby unit (SCBU) at National Health Service Foundation Trust Cambridge, UK. used validate expand findings from an...

10.1016/s1473-3099(12)70268-2 article EN cc-by The Lancet Infectious Diseases 2012-11-14

In cell‐free Pseudomonas aeruginosa culture supernatants, we identified two compounds capable of activating an N ‐acylhomoserine lactone (AHL) biosensor. Mass spectrometry and NMR spectroscopy revealed that these were not AHLs but the diketopiperazines (DKPs), cyclo(ΔAla‐ l ‐Val) cyclo( ‐Pro‐ ‐Tyr) respectively. These also found in supernatants from Proteus mirabilis , Citrobacter freundii Enterobacter agglomerans [cyclo(ΔAla‐ only]. Although both DKPs absent fluorescens alcaligenes...

10.1046/j.1365-2958.1999.01577.x article EN Molecular Microbiology 1999-09-01
Brian J. Willett Joe Grove Oscar A. MacLean Craig Wilkie Giuditta De Lorenzo and 95 more Wilhelm Furnon Diego Cantoni Sam Scott Nicola Logan Shirin Ashraf Maria Manali Agnieszka M. Szemiel Vanessa M. Cowton Elen Vink William T. Harvey Christopher Davis Patawee Asamaphan Katherine Smollett L. Tong Richard Orton Joseph Hughes Poppy Holland Vanessa Silva David J. Pascall Kathryn Puxty Ana da Silva Filipe Gonzalo Yebra Sharif Shaaban Matthew T. G. Holden Rute Maria Pinto Rory Gunson Kate Templeton Pablo R. Murcia Arvind H. Patel Paul Klenerman Susanna Dunachie Susanna Dunachie Paul Klenerman Eleanor Barnes Anthony Brown Sandra Adele Barbara Kronsteiner Sam M. Murray Priyanka Abraham Alexandra Deeks M. Azim Ansari Thushan I. de Silva Lance Turtle Shona C. Moore James Austin Alex Richter C.J. Duncan Rebecca P. Payne Amy Ash Cherian Koshy Beatrix Kele Teresa Cutiño‐Moguel Derek Fairley James P. McKenna Tanya Curran Helen Adams Christophe Fraser David Bonsall Helen Fryer Katrina Lythgoe Emma C. Thomson Tanya Golubchik Abigail Murray Dawn Singleton Shaun M. Beckwith Anna Mantzouratou Magdalena Barrow Sarah L. Buchan Nicola Reynolds Ben Warne Joshua Maksimovic Karla Spellman Kathryn McCluggage John P.T. Mo Robert Beer Safiah Afifi Sian Morgan Andrew Mack Angela Marchbank Anna Price Arthur Morriss Catherine Bresner Christine Kitchen Ian Merrick Joel Southgate Martyn F. Guest Owen Jones Robert J. Munn Thomas R. Connor Thomas Whalley Trudy Workman William Fuller Amita Patel Bindi Patel Gaia Nebbia

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone public health response to COVID-19. The emergence hypermutated, increasingly transmissible variants concern (VOCs) threaten this strategy. Omicron (B.1.1.529), fifth VOC be described, harbours multiple amino acid mutations in spike, half which lie within receptor-binding domain. Here we demonstrate substantial evasion neutralization by BA.1 and BA.2 vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2...

10.1038/s41564-022-01143-7 article EN cc-by Nature Microbiology 2022-07-07

The widespread use of antibiotics in association with high-density clinical care has driven the emergence drug-resistant bacteria that are adapted to thrive hospitalized patients. Of particular concern globally disseminated methicillin-resistant Staphylococcus aureus (MRSA) clones cause outbreaks and epidemics associated health care. most rapidly spreading tenacious health-care-associated clone Europe currently is EMRSA-15, which was first detected UK early 1990s subsequently spread...

10.1101/gr.147710.112 article EN cc-by-nc Genome Research 2013-01-08
Bo Meng Steven A. Kemp Guido Papa Rawlings Datir Isabella A. T. M. Ferreira and 95 more Sara Marelli William T. Harvey Spyros Lytras Ahmed Mohamed Giulia Gallo Nazia Thakur Dami A. Collier Petra Mlčochová Samuel C. Robson Nicholas J. Loman Thomas R. Connor Tanya Golubchik Rocio T. Martinez Nunez Catherine Ludden Sally Corden Ian Johnston David Bonsall Colin P. Smith Ali Raza Awan Giselda Bucca M. Estée Török Kordo Saeed Jacqui Prieto David K. Jackson William L. Hamilton Luke B. Snell Catherine Moore Ewan M. Harrison Sónia Gonçalves Derek Fairley Matthew Loose Joanne Watkins Rich Livett Samuel Moses Roberto Amato Samuel M. Nicholls Matthew Bull Darren Smith Jeff Barrett David M. Aanensen Martin D. Curran Surendra Parmar Dinesh Aggarwal James G. Shepherd Matthew D. Parker Sharon Glaysher Matthew Bashton Anthony P. Underwood Nicole Pacchiarini Katie F. Loveson Kate Templeton Cordelia F. Langford John Sillitoe Thushan I. de Silva Dennis Wang Dominic Kwiatkowski Andrew Rambaut Justin O’Grady Simon Cottrell Matthew T. G. Holden Emma C. Thomson Husam Osman Monique Andersson Anoop Chauhan Mohammed O. Hassan-Ibrahim Mara Lawniczak Alex Alderton Meera Chand Chrystala Constantinidou Meera Unnikrishnan Alistair C. Darby Julian A. Hiscox Steve Paterson Inigo Martincorena Erik Volz Andrew J. Page Oliver G. Pybus Andrew R. Bassett Cristina V. Ariani Michael H. Spencer Chapman Kathy K. Li Rajiv Shah Natasha Jesudason Yusri Taha M. McHugh Rebecca Dewar Aminu S. Jahun Claire McMurray Sarojini Pandey James McKenna Andrew Nelson Gregory R. Young Clare M. McCann Scott Elliott Hannah Lowe

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike ΔH69/V70 in multiple independent lineages, often occurring after acquisition of receptor binding motif replacements such as N439K and Y453F, known to increase affinity the ACE2 confer antibody escape. In vitro, we show that, although itself is not an evasion mechanism, it increases infectivity associated with enhanced incorporation cleaved into virions. able partially rescue proteins that have acquired Y453F escape...

10.1016/j.celrep.2021.109292 article EN cc-by Cell Reports 2021-06-01

The bacterial family Enterobacteriaceae is notable for its well studied human pathogens, including Salmonella , Yersinia Shigella and Escherichia spp. However, it also contains several plant pathogens. We report the genome sequence of a pathogenic enterobacterium, Erwinia carotovora subsp. atroseptica ( Eca ) strain SCRI1043, causative agent soft rot blackleg potato diseases. Approximately 33% genes are not shared with sequenced enterobacterial some predicted to facilitate unexpected...

10.1073/pnas.0402424101 article EN Proceedings of the National Academy of Sciences 2004-07-19

ABSTRACT Bacterial infections of the lungs cystic fibrosis (CF) patients cause major complications in treatment this common genetic disease. Burkholderia cenocepacia infection is particularly problematic since organism has high levels antibiotic resistance, making it difficult to eradicate; resulting chronic are associated with severe declines lung function and increased mortality rates. B. strain J2315 was isolated from a CF patient member epidemic ET12 lineage that originated Canada or...

10.1128/jb.01230-08 article EN Journal of Bacteriology 2008-10-18

The spread of drug-resistant bacterial pathogens poses a major threat to global health. It is widely recognised that the widespread use antibiotics has generated selective pressures have driven emergence resistant strains. Methicillin-resistant Staphylococcus aureus (MRSA) was first observed in 1960, less than one year after introduction this second generation beta-lactam antibiotic into clinical practice. Epidemiological evidence always suggested resistance arose around period, when mecA...

10.1186/s13059-017-1252-9 article EN cc-by Genome biology 2017-07-06

GeneDB (http://www.genedb.org) is a genome database for prokaryotic and eukaryotic pathogens closely related organisms. The resource provides portal to sequence annotation data, which primarily generated by the Pathogen Genomics group at Wellcome Trust Sanger Institute. It combines data from completed ongoing projects with curated annotation, readily accessible web based resource. development of in recent years has focused on providing database-driven tools pipelines, as well catering...

10.1093/nar/gkr1032 article EN cc-by-nc Nucleic Acids Research 2011-11-23
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