Professor Stephen D. Bentley | Principal Staff Scientist and Team Leader

Bentley, Stephen D.

Using bacterial pathogen genomics to understand patterns of colonisation, transmission and genetic associations with disease. Focus on pathogens associated with respiratory infection and particularly those which have a major disease burden in resource-poor settings.

Stephen joined the Sanger Institute in 1998 to work on the annotation and analysis of bacterial genomes. His early work focused on the antibiotic-producing soil bacterium Streptomyces coelicolor and the rare human pathogen Tropheryma whipplei and provided insights into the mechanisms of horizontal gene transfer, generation of antigenic variation and the prevalence of antibiotic production genes. This was followed by research into Streptococcus pneumoniae and Neisseria meningitidis showing that gene and genome variation between loci and species was due to common and differing mechanisms of variation. The study to sequence the capsular biosynthesis genes for all known serotypes of S. pneumoniae enabled molecular methods for determining serotype which have brought important new understanding of pneumococcal colonisation and transmission.

Since the development of high throughput sequencing Stephen's research has focused on population genomics with pioneering papers on MRSA (2010) and the pneumococcus (2011) revealing patterns of international spread, vaccine escape and the aquisition of antimicrobial resistance.

Publications

  • Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study.

    Lo SW, Gladstone RA, van Tonder AJ, Lees JA, du Plessis M et al.

    The Lancet. Infectious diseases 2019;19;7;759-769

  • Evolution of MRSA during hospital transmission and intercontinental spread.

    Harris SR, Feil EJ, Holden MT, Quail MA, Nickerson EK et al.

    Science (New York, N.Y.) 2010;327;5964;469-74

  • Rapid pneumococcal evolution in response to clinical interventions.

    Croucher NJ, Harris SR, Fraser C, Quail MA, Burton J et al.

    Science (New York, N.Y.) 2011;331;6016;430-4

  • Dense genomic sampling identifies highways of pneumococcal recombination.

    Chewapreecha C, Harris SR, Croucher NJ, Turner C, Marttinen P et al.

    Nature genetics 2014;46;3;305-309

  • Population genomics of post-vaccine changes in pneumococcal epidemiology.

    Croucher NJ, Finkelstein JA, Pelton SI, Mitchell PK, Lee GM et al.

    Nature genetics 2013;45;6;656-63

  • Whole-genome sequencing for analysis of an outbreak of meticillin-resistant Staphylococcus aureus: a descriptive study.

    Harris SR, Cartwright EJ, Török ME, Holden MT, Brown NM et al.

    The Lancet. Infectious diseases 2013;13;2;130-6

  • Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes.

    Bentley SD, Aanensen DM, Mavroidi A, Saunders D, Rabbinowitsch E et al.

    PLoS genetics 2006;2;3;e31

  • Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

    Bentley SD, Chater KF, Cerdeño-Tárraga AM, Challis GL, Thomson NR et al.

    Nature 2002;417;6885;141-7

  • Synergistic Activity of Mobile Genetic Element Defences in Streptococcus pneumoniae.

    Kwun MJ, Oggioni MR, Bentley SD, Fraser C and Croucher NJ

    Genes 2019;10;9

  • Recombination of the Phase-Variable spnIII Locus Is Independent of All Known Pneumococcal Site-Specific Recombinases.

    De Ste Croix M, Chen KY, Vacca I, Manso AS, Johnston C et al.

    Journal of bacteriology 2019;201;15

  • Genome-wide epistasis and co-selection study using mutual information.

    Pensar J, Puranen S, Arnold B, MacAlasdair N, Kuronen J et al.

    Nucleic acids research 2019

  • The impact of antimicrobials on gonococcal evolution.

    Sánchez-Busó L, Golparian D, Corander J, Grad YH, Ohnishi M et al.

    Nature microbiology 2019

  • Methylation warfare: interaction of pneumococcal bacteriophages with their host.

    Furi L, Crawford LA, Rangel-Pineros G, Manso AS, De Ste Croix M et al.

    Journal of bacteriology 2019

  • Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study.

    Lo SW, Gladstone RA, van Tonder AJ, Lees JA, du Plessis M et al.

    The Lancet. Infectious diseases 2019;19;7;759-769

  • Putative novel cps loci in a large global collection of pneumococci.

    van Tonder AJ, Gladstone RA, Lo SW, Nahm MH, du Plessis M et al.

    Microbial genomics 2019;5;7

  • Fast hierarchical Bayesian analysis of population structure.

    Tonkin-Hill G, Lees JA, Bentley SD, Frost SDW and Corander J

    Nucleic acids research 2019;47;11;5539-5549

  • Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

    Davies MR, McIntyre L, Mutreja A, Lacey JA, Lees JA et al.

    Nature genetics 2019;51;6;1035-1043

  • Early signals of vaccine driven perturbation seen in pneumococcal carriage population genomic data.

    Chaguza C, Heinsbroek E, Gladstone RA, Tafatatha T, Alaerts M et al.

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2019

  • Joint sequencing of human and pathogen genomes reveals the genetics of pneumococcal meningitis.

    Lees JA, Ferwerda B, Kremer PHC, Wheeler NE, Serón MV et al.

    Nature communications 2019;10;1;2176

  • International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact.

    Gladstone RA, Lo SW, Lees JA, Croucher NJ, van Tonder AJ et al.

    EBioMedicine 2019;43;338-346

  • PANINI: Pangenome Neighbour Identification for Bacterial Populations.

    Abudahab K, Prada JM, Yang Z, Bentley SD, Croucher NJ et al.

    Microbial genomics 2019;5;4

  • Fast and flexible bacterial genomic epidemiology with PopPUNK.

    Lees JA, Harris SR, Tonkin-Hill G, Gladstone RA, Lo SW et al.

    Genome research 2019;29;2;304-316

  • Vaccination of Icelandic children with the 10-valent pneumococcal vaccine leads to a significant herd effect among adults in Iceland.

    Quirk SJ, Haraldsson G, Hjálmarsdóttir MÁ, van Tonder AJ, Hrafnkelsson B et al.

    Journal of clinical microbiology 2019

  • The Contribution of Genetic Variation of Streptococcus pneumoniae to the Clinical Manifestation of Invasive Pneumococcal Disease.

    Cremers AJH, Mobegi FM, van der Gaast-de Jongh C, van Weert M, van Opzeeland FJ et al.

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2019;68;1;61-69

  • Genomic Analyses of >3,100 Nasopharyngeal Pneumococci Revealed Significant Differences Between Pneumococci Recovered in Four Different Geographical Regions.

    van Tonder AJ, Bray JE, Jolley KA, Jansen van Rensburg M, Quirk SJ et al.

    Frontiers in microbiology 2019;10;317

  • DORA Editorial.

    Parish T, Harris M, Fry N, Mathee K, Trujillo ME et al.

    Microbiology (Reading, England) 2018

  • Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci.

    Azarian T, Mitchell PK, Georgieva M, Thompson CM, Ghouila A et al.

    PLoS pathogens 2018;14;11;e1007438

  • Excision-reintegration at a pneumococcal phase-variable restriction-modification locus drives within- and between-strain epigenetic differentiation and inhibits gene acquisition.

    Kwun MJ, Oggioni MR, De Ste Croix M, Bentley SD and Croucher NJ

    Nucleic acids research 2018

  • Effect of vaccination on pneumococci isolated from the nasopharynx of healthy children and the middle ear of children with otitis media in Iceland.

    Quirk SJ, Haraldsson G, Erlendsdóttir H, Hjálmarsdóttir MÁ, van Tonder AJ et al.

    Journal of clinical microbiology 2018

  • Pneumococcal Vaccines: Host Interactions, Population Dynamics, and Design Principles.

    Croucher NJ, Løchen A and Bentley SD

    Annual review of microbiology 2018;72;521-549

  • Bayesian inference of ancestral dates on bacterial phylogenetic trees.

    Didelot X, Croucher NJ, Bentley SD, Harris SR and Wilson DJ

    Nucleic acids research 2018

  • Pneumococcal vaccine impacts on the population genomics of non-typeable Haemophilus influenzae.

    Cleary D, Devine V, Morris D, Osman K, Gladstone R et al.

    Microbial genomics 2018

  • Loss of genomic diversity in a Neisseria meningitidis clone through a colonization bottleneck.

    Lamelas A, Hamid AM, Dangy JP, Hauser J, Jud M et al.

    Genome biology and evolution 2018

  • Global Distribution of Invasive Serotype 35D Streptococcus pneumoniae Isolates following Introduction of 13-Valent Pneumococcal Conjugate Vaccine.

    Lo SW, Gladstone RA, van Tonder AJ, Hawkins PA, Kwambana-Adams B et al.

    Journal of clinical microbiology 2018;56;7

  • SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data.

    Epping L, van Tonder AJ, Gladstone RA, The Global Pneumococcal Sequencing Consortium, Bentley SD et al.

    Microbial genomics 2018

  • SuperDCA for genome-wide epistasis analysis.

    Puranen S, Pesonen M, Pensar J, Xu YY, Lees JA et al.

    Microbial genomics 2018;4;6

  • The impact of serotype-specific vaccination on phylodynamic parameters of Streptococcus pneumoniae and the pneumococcal pan-genome.

    Azarian T, Grant LR, Arnold BJ, Hammitt LL, Reid R et al.

    PLoS pathogens 2018;14;4;e1006966

  • The effect of environmental and management associated factors on prevalence and diversity ofStreptococcus suisin clinically healthy pig herds of China and UK.

    Zou G, Zhou J, Xiao R, Zhang L, Cheng Y et al.

    Applied and environmental microbiology 2018

  • Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study.

    Lees JA, Kendall M, Parkhill J, Colijn C, Bentley SD and Harris SR

    Wellcome open research 2018;3;33

  • Global Scale Dissemination of ST93: A Divergent Staphylococcus aureus Epidemic Lineage That Has Recently Emerged From Remote Northern Australia.

    van Hal SJ, Steinig EJ, Andersson P, Holden MTG, Harris SR et al.

    Frontiers in microbiology 2018;9;1453

  • RhierBAPS: An R implementation of the population clustering algorithm hierBAPS.

    Tonkin-Hill G, Lees JA, Bentley SD, Frost SDW and Corander J

    Wellcome open research 2018;3;93

  • Whole-Genome Sequencing for Routine Pathogen Surveillance in Public Health: a Population Snapshot of Invasive Staphylococcus aureus in Europe.

    Aanensen DM, Feil EJ, Holden MT, Dordel J, Yeats CA et al.

    mBio 2016;7;3

  • Evidence of antimicrobial resistance-conferring genetic elements among pneumococci isolated prior to 1974.

    Wyres KL, van Tonder A, Lambertsen LM, Hakenbeck R, Parkhill J et al.

    BMC genomics 2013;14;500

Bentley, Stephen D.