ClaireTurner - People - Molecular Biology and Biotechnology

Dr Claire Turner

Research Fellow

Tel: 0114 222 2819
Email: c.e.turner@sheffield.ac.uk

Research	Research Precis My research focus is on trying to understand the mechanisms behind upsurges in disease caused by the human pathogen Streptococcus pyogenes (also known as group A Streptococcus). Upsurges occur frequently and can be associated with specific genotypes. I use a combination of whole genome sequencing, epidemiology, clinical analysis and phenotypic work to try and identify what makes strains successful at causing disease and become suddenly more abundant. One of my particular interests is recombination-related genome remodelling, which we identified to be the driving force behind a very recent shift in the population of the S. pyogenes genotype emm89. A new variant of emm89 emerged from the population having undergone six regions of recombination within the core genome. This recombination-related genome remodelling led to substantial phenotype changes, including loss of the hyaluronic acid capsule and increase of toxin expression, altering the way this genotype interacted with the host. The emergent variant has now become the dominant form of emm89 in the UK and globally, causing a high level of disease. Understanding how recombination occurs and what the impact of recombination is on the bacterium are part of my research aims. Figure 1. Whole genome sequencing of 131 isolates of emm89 S. pyogenes from the UK identified an emergent clade variant that differed from the rest of the population of emm89 S. pyogenes by a high number of SNPs. This high level of variation is unexpected within a genotype but, importantly, the majority of the SNPs actually clustered in to six regions within the genome, which is indicative of recombination. Figure 2. (A) The largest region of recombination with emm89 encompassed the toxin genes nga and slo, which encode for NADase and Streptolysin O, and when combined can be lethal to host cells. These toxins are also thought to promote survival of S. pyogenes inside host cells. Compared to the previous variant, this region in the emergent variant contained a high number of SNPs (indicated by vertical lines; black = synonymous, red = non-synonymous) indicating that this region had been obtained from an external donor. (B) The expression of nga was high in the emergent variant (red) compared to nearly undetectable levels in the previous emm89 variant (blue). Research Keywords Microbiology, Streptococcus pyogenes, Group A streptococcus, bacterial evolution, scarlet fever, necrotising fasciitis, tonsilitis, whole genome sequencing, recombination.
Teaching
Career History	Career History 2017-present: Royal Society/ Wellcome Trust Sir Henry Dale Research Fellow, University of Sheffield. 2017-present: Florey Institute Research Fellow, University of Sheffield 2013-2016: Imperial College Junior Research Fellow 2009-2013: Research Associate, National Centre for Infection Prevention & Management, Imperial College London 2005-2009: PhD, Imperial College London.

Research

Research Precis

fig1 My research focus is on trying to understand the mechanisms behind upsurges in disease caused by the human pathogen Streptococcus pyogenes (also known as group A Streptococcus). Upsurges occur frequently and can be associated with specific genotypes. I use a combination of whole genome sequencing, epidemiology, clinical analysis and phenotypic work to try and identify what makes strains successful at causing disease and become suddenly more abundant.
One of my particular interests is recombination-related genome remodelling, which we identified to be the driving force behind a very recent shift in the population of the S. pyogenes genotype emm89. A new variant of emm89 emerged from the population having undergone six regions of recombination within the core genome. This recombination-related genome remodelling led to substantial phenotype changes, including loss of the hyaluronic acid capsule and increase of toxin expression, altering the way this genotype interacted with the host. The emergent variant has now become the dominant form of emm89 in the UK and globally, causing a high level of disease. Understanding how recombination occurs and what the impact of recombination is on the bacterium are part of my research aims.

Figure 1. Whole genome sequencing of 131 isolates of emm89 S. pyogenes from the UK identified an emergent clade variant that differed from the rest of the population of emm89 S. pyogenes by a high number of SNPs. This high level of variation is unexpected within a genotype but, importantly, the majority of the SNPs actually clustered in to six regions within the genome, which is indicative of recombination.

fig2

Figure 2. (A) The largest region of recombination with emm89 encompassed the toxin genes nga and slo, which encode for NADase and Streptolysin O, and when combined can be lethal to host cells. These toxins are also thought to promote survival of S. pyogenes inside host cells. Compared to the previous variant, this region in the emergent variant contained a high number of SNPs (indicated by vertical lines; black = synonymous, red = non-synonymous) indicating that this region had been obtained from an external donor. (B) The expression of nga was high in the emergent variant (red) compared to nearly undetectable levels in the previous emm89 variant (blue).

Research Keywords

Microbiology, Streptococcus pyogenes, Group A streptococcus, bacterial evolution, scarlet fever, necrotising fasciitis, tonsilitis, whole genome sequencing, recombination.

Teaching

Career History

            2017-present: Royal Society/ Wellcome Trust Sir Henry Dale Research Fellow, University of Sheffield.
2017-present: Florey Institute Research Fellow, University of Sheffield
2013-2016:	Imperial College Junior Research Fellow
2009-2013:	Research Associate, National Centre for Infection Prevention & Management, Imperial College London
2005-2009:	PhD, Imperial College London.

            

Journal articles

Armitage EP, Senghore E, Darboe S, Barry M, Camara J, Bah S, Marks M, Cerami C, Roca A, Antonio M , Turner CE et al (2019) High burden and seasonal variation of paediatric scabies and pyoderma prevalence in The Gambia: A cross-sectional study.. PLoS Negl Trop Dis, 13(10), e0007801.
Sharma H, Turner CE, Siggins MK, El-Bahrawy M, Pichon B, Kearns A & Sriskandan S (2019) Toxic Shock Syndrome Toxin 1 Evaluation and Antibiotic Impact in a Transgenic Model of Staphylococcal Soft Tissue Infection.. mSphere, 4(5).
Lynskey NN, Jauneikaite E, Li HK, Zhi X, Turner CE, Mosavie M, Pearson M, Asai M, Lobkowicz L, Chow JY , Parkhill J et al (2019) Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study. The Lancet Infectious Diseases.
Turner CE, Bubba L & Efstratiou A (2019) Pathogenicity Factors in Group C and G Streptococci. Microbiology Spectrum, 7(3).
Davies FJ, Olme C, Lynskey NN, Turner CE & Sriskandan S (2019) Streptococcal superantigen‐induced expansion of human tonsil T cells leads to altered T follicular helper cell phenotype, B cell death and reduced immunoglobulin release. Clinical & Experimental Immunology. View this article in WRRO
Reglinski M, Sriskandan S & Turner C (2019) Identification of two new core chromosome-encoded superantigens in Streptococcus pyogenes; speQ and speR. Journal of Infection. View this article in WRRO
Lamb LE, Siggins MK, Scudamore C, Macdonald W, Turner CE, Lynskey NN, Tan LKK & Sriskandan S (2018) Impact of contusion injury on intramuscular emm1 group a streptococcus infection and lymphatic spread. Virulence, 9(1), 1074-1084. View this article in WRRO
Edwards RJ, Pyzio M, Gierula M, Turner CE, Abdul-Salam VB & Sriskandan S (2018) Proteomic analysis at the sites of clinical infection with invasive Streptococcus pyogenes. Scientific Reports, 8(1). View this article in WRRO
Remmington A & Turner CE (2018) The DNases of pathogenic Lancefield streptococci.. Microbiology, 164(3), 242-250. View this article in WRRO
Sharma H, Smith D, Turner CE, Game L, Pichon B, Hope R, Hill R, Kearns A & Sriskandan S (2018) Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the United Kingdom. Emerging Infectious Diseases, 24(2). View this article in WRRO
Turner CE, Bedford L, Brown NM, Judge K, Török ME, Parkhill J & Peacock SJ (2017) Community outbreaks of group A Streptococcus revealed by genome sequencing. Scientific Reports, 7(1). View this article in WRRO
Afshar B, Turner CE, Lamagni T, Smith K, Al-Shahib A, Underwood A, Holden M, Efstratiou A & Sriskandan S (2017) Enhanced nasopharyngeal infection and shedding associated with an epidemic lineage of emm3 group A Streptococcus. Virulence, 8(7), 1390-1400. View this article in WRRO
Al-Shahib A, Underwood A, Afshar B, Turner CE, Lamagni T, Sriskandan S & Efstratiou A (2016) Corrigendum: Emergence of a novel lineage containing a prophage in emm/M3 group A Streptococcus associated with upsurge in invasive disease in the UK. Microbial Genomics, 2(11).
Al-Shahib A, Underwood A, Afshar B, Turner CE, Lamagni T, Sriskandan S & Efstratiou A (2016) Emergence of a novel lineage containing a prophage in emm/M3 group A Streptococcus associated with upsurge in invasive disease in the UK. Microbial Genomics, 2(6). View this article in WRRO
Turner CE, Pyzio M, Song B, Lamagni T, Meltzer M, Chow JY, Efstratiou A, Curtis S & Sriskandan S (2016) Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014. Emerging Infectious Diseases, 22(6), 1075-1078.
Smith DS, Siggins MK, Gierula M, Pichon B, Turner CE, Lynskey NN, Mosavie M, Kearns AM, Edwards RJ & Sriskandan S (2016) Identification of commonly expressed exoproteins and proteolytic cleavage events by proteomic mining of clinically relevant UK isolates of Staphylococcus aureus. Microbial Genomics, 2(2). View this article in WRRO
Lamb L, MacDonald W, Scudamore C, Tan L, Lynskey N, Turner CE & Sriskandan S (2015) The effect of trauma on invasive group A streptococcal (IGAS) disease. Journal of Infection, 71(6), 686-686.
Turner CE & Sriskandan S (2015) Panton–Valentine leucocidin expression by Staphylococcus aureus exposed to common antibiotics. Journal of Infection, 71(3), 338-346.
Lynskey NN, Turner CE, Heng LS & Sriskandan S (2015) A Truncation in the Regulator RocA Underlies Heightened Capsule Expression in Serotype M3 Group A Streptococci. Infection and Immunity, 83(4), 1732-1733. View this article in WRRO
Turner CE, Dryden M, Holden MTG, Davies FJ, Lawrenson RA, Farzaneh L, Bentley SD, Efstratiou A & Sriskandan S (2013) Molecular Analysis of an Outbreak of Lethal Postpartum Sepsis Caused by Streptococcus pyogenes. Journal of Clinical Microbiology, 51(7), 2089-2095. View this article in WRRO
Davies F, Turner C, Boyle J & Sriskandan S (2010) Streptococcus pyogenes superantigen SPEA expression suppresses all immunoglobulin classes in human tonsil explants. Journal of Infection, 61(6), 518-518.
(2009) ERRATUM. The Journal of Infectious Diseases, 200(8), 1353-1353.
Turner CE, Kurupati P, Jones MD, Edwards RJ & Sriskandan S (2009) Emerging Role of the Interleukin‐8 Cleaving Enzyme SpyCEP in ClinicalStreptococcus pyogenesInfection. The Journal of Infectious Diseases, 200(4), 555-563.
Turner CE, Kurupati P, Wiles S, Edwards RJ & Sriskandan S (2009) Impact of immunization against SpyCEP during invasive disease with two streptococcal species: Streptococcus pyogenes and Streptococcus equi. Vaccine, 27(36), 4923-4929.
Zinkernagel AS, Timmer AM, Pence MA, Locke JB, Buchanan JT, Turner CE, Mishalian I, Sriskandan S, Hanski E & Nizet V (2008) The IL-8 Protease SpyCEP/ScpC of Group A Streptococcus Promotes Resistance to Neutrophil Killing. Cell Host & Microbe, 4(2), 170-178.
Turner C & Sriskandan S (2007) Streptococcus pyogenes under pressure. Nature Medicine, 13(8), 909-910.
Edwards RJ, Taylor GW, Ferguson M, Murray S, Rendell N, Wrigley A, Bai Z, Boyle J, Finney SJ, Jones A , Russell HH et al (2005) Specific C‐Terminal Cleavage and Inactivation of Interleukin‐8 by Invasive Disease Isolates ofStreptococcus pyogenes. The Journal of Infectious Diseases, 192(5), 783-790.
Turner CE, Lamagni T, Holden MTG, David S, Jones MD, Game L, Efstratiou A & Sriskandan S () Turner et al. Reply to “Emergence of the Same Successful Clade among Distinct Populations of emm89 Streptococcus pyogenes in Multiple Geographic Regions”. mBio, 6(6). View this article in WRRO
Turner CE, Abbott J, Lamagni T, Holden MTG, David S, Jones MD, Game L, Efstratiou A & Sriskandan S () Emergence of a New Highly Successful Acapsular Group A Streptococcus Clade of Genotype emm89 in the United Kingdom. mBio, 6(4). View this article in WRRO
Lynskey NN, Goulding D, Gierula M, Turner CE, Dougan G, Edwards RJ & Sriskandan S () RocA Truncation Underpins Hyper-Encapsulation, Carriage Longevity and Transmissibility of Serotype M18 Group A Streptococci. PLoS Pathogens, 9(12), e1003842-e1003842.
Alam FM, Bateman C, Turner CE, Wiles S & Sriskandan S () Non-Invasive Monitoring of Streptococcus pyogenes Vaccine Efficacy Using Biophotonic Imaging. PLoS ONE, 8(11), e82123-e82123. View this article in WRRO
Alam FM, Turner CE, Smith K, Wiles S & Sriskandan S () Correction: Inactivation of the CovR/S Virulence Regulator Impairs Infection in an Improved Murine Model of Streptococcus pyogenes Naso-Pharyngeal Infection. PLoS ONE, 8(9).
Alam FM, Turner CE, Smith K, Wiles S & Sriskandan S () Inactivation of the CovR/S Virulence Regulator Impairs Infection in an Improved Murine Model of Streptococcus pyogenes Naso-Pharyngeal Infection. PLoS ONE, 8(4), e61655-e61655.
Turner CE, Sommerlad M, McGregor K, Davies FJ, Pichon B, Chong DLW, Farzaneh L, Holden MTG, Spratt BG, Efstratiou A & Sriskandan S () Superantigenic Activity of emm3 Streptococcus pyogenes Is Abrogated by a Conserved, Naturally Occurring smeZ Mutation. PLoS ONE, 7(10), e46376-e46376. View this article in WRRO
Kurupati P, Turner CE, Tziona I, Lawrenson RA, Alam FM, Nohadani M, Stamp GW, Zinkernagel AS, Nizet V, Edwards RJ & Sriskandan S () Chemokine-cleaving Streptococcus pyogenes protease SpyCEP is necessary and sufficient for bacterial dissemination within soft tissues and the respiratory tract. Molecular Microbiology, 76(6), 1387-1397.
Siggins M, Lynskey NN, Lamb LE, Johnson LA, Huse KK, Pearson M, Banerji S, Turner CE, Woollard K, Jackson DG & Sriskandan S () Lymphatic Metastasis of Virulent Extracellular Bacteria Drives Systemic Infection. SSRN Electronic Journal. View this article in WRRO

Chapters

Efstratiou A, Lamagni T & Turner CE (2017) Streptococci and Enterococci, Infectious Diseases (pp. 1523-1536.e2). Elsevier
Efstratiou A, Lamagni T & Turner CE (2016) Streptococci and Enterococci In Cohen J, Powderly W & Opal S (Ed.), Infectious Diseases 4th edition Elsevier