Imperial College London

ProfessorShiraneeSriskandan

Faculty of MedicineDepartment of Infectious Disease

Professor of Infectious Diseases
 
 
 
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Contact

 

s.sriskandan

 
 
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Assistant

 

Ms Teyanna Gaeta +44 (0)20 3313 1943

 
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Location

 

8N21ACWBHammersmith HospitalHammersmith Campus

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Summary

 

Summary

Gram Positive Pathogenesis

We research the mechanisms by which Gram positive bacteria cause disease, using the group A streptococcus (Streptococcus pyogenes) as a paradigm. Based in the Section of Adult Infectious Disease, the group is also part of the MRC Centre for Molecular Bacteriology & Infection (CMBI) and the NIHR Health Protection Research Unit (HPRU) in Healthcare Associated Infection and Antimicrobial Resistance.


Group A strep on agar (Photo: David Goulding WTSI)S. pyogenes causes a spectrum of disease ranging from pharyngitis to invasive infections such as necrotising fasciitis, maternal sepsis, and toxic shock. In the developing world, S. pyogenes is associated with rheumatic fever, a major cause of valvular heart disease. Despite the burden of illness, there is no vaccine, a deficiency highlighted by WHO.

Our research examines the relation between pathogen and host immune response, and is driven by changes we observe in the bacteria, the infection severity in patients, and epidemiological changes in disease over time. This has led to our current work on novel proteases that might function as vaccine targets, unexpected routes of bacterial dissemination in the lymphatic system, and recognition that large and small scale genome remodelling may have major impacts on disease frequency. We are learning that changes in the environment and human behaviour might also impact on bacterial and disease phenotypes.

SMEZ-2, courtesy Prof Ted Baker, Univ of Auckland

One of our interests is the role of bacterial superantigens in streptococcal disease, in particular the classical phage-encoded scarlet fever toxins, SPEA  and SPEC, which, like the staphylococcal superantigens  can trigger toxic shock but may also play an important role in perpetuating outbreaks of S. pyogenes in the community, in particular scarlet fever.

Cleavage of CXCL8 by SpyCEP

Evasion of the innate immune response is a trademark of S. pyogenes and we have a longstanding interest in the CXC-chemokine cleaving protease SpyCEP (cepA) and the homologue C5a peptidase (scpA) that cleaves C3a and C5a. Proteases like these, that are conserved, may provide excellent vaccine targets. 

Recently we have been trying to understand how S. pyogenes might spread from a non-invasive focus of infection to the bloodstream and have identified that extracellular bacteria can metastasise in the lymphatic system to reach the blood circulation.

RESEARCH THAT IMPACTS ON PUBLIC HEALTH

 

Prof. Sriskandan has a longstanding collaboration with Public Health England and the group's research reflects a focus on understanding trends in streptococcal disease to inform interventions that might improve public health. As theme lead for ‘Applied Molecular Bacteriology’ in the NIHR Health Protection Research Unit (HPRU) in Healthcare Associated Infection and Antimicrobial Resistance,  her group has examined the molecular basis for bacterial infections relevant to the healthcare setting, such as Escherichia coli bacteremia, antimicrobial resistance, and haemolytic streptococal infections that are of public health importance. The HPRU, which was established on 1 April 2014, is a partnership between Imperial College London, Public Health England, Cambridge University Veterinary School, the Wellcome Trust Sanger Institute (WTSI) and Imperial College Health Partners.

CURRENT PROJECTS


  • Puerperal sepsis and the Colebrooks (see 'Research' tab)
  • SpyCEP and C5a peptidase - Wellcome Trust Collaborative grant with Steve Matthews (CMBI/Life Sciences) and James Pease (NHLI)
  • Molecular anatomy of S. pyogenes and scarlet fever  in UK (MRC project in collaboration with PHE)
  • Transmission of S. pyogenes during scarlet fever outbreaks (Action Medical Research project with PHE)
  • S. pyogenes capsule and lymphatic system metastasis (MRC project  with David Jackson, University of Oxford)
  • BioAID Biobank for adult infectious diseases  (Cross- BRC Collaboration with UCLH, Mahdad Noursadeghi; Imperial colleagues Graham Cooke, Hugo Donaldson)
  • Molecular basis for upsurge in E. coli bacteremia, genomics, nitrofurantoin resistance (HPRU collaboration with PHE)
  • Group B streptococcus nosocomial spread (HPRU collaboration with PHE)

Recent Collaborations

  • University of Lund (Lars Bjork and Inga-Maria Frick)  - Protein SIC
  • University of Auckland (Siouxsie Wiles, John Fraser and Thomas Proft)
  • Wellcome Trust Sanger Institute (Julian Parkhill, David Goulding)
  • University of Cambridge (Sharon Peacock)
  • University of Sheffield (Claire E. Turner)

Selected Publications

Journal Articles

Siggins MK, Lynskey NN, Lamb L, et al., 2020, Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection, Nature Communications, Vol:11, ISSN:2041-1723

Lynskey NN, Jauneikaite E, Li H-K, et al., 2019, Emergence of dominant toxigenic M1T1 Streptococcus pyogenes clone during increased scarlet fever activity in England: a population-based molecular epidemiological study, Lancet Infectious Diseases, Vol:19, ISSN:1473-3099, Pages:1209-1218

Turner CE, Holden MTG, Blane B, et al., 2019, The emergence of successful streptococcus pyogenes lineages through convergent pathways of capsule loss and recombination directing high toxin expression, MBIO, Vol:10, ISSN:2150-7511, Pages:1-20

Jauneikaite E, Kapatai G, Davies F, et al., 2018, Serial clustering of late onset group B streptococcal infections in the neonatal unit - a genomic re-evaluation of causality, Clinical Infectious Diseases, Vol:67, ISSN:1058-4838, Pages:854-860

Sharma H, Smith D, Turner CE, et al., 2018, Clinical and Molecular Epidemiology of Staphylococcal Toxic Shock Syndrome in the United Kingdom, Emerging Infectious Diseases, Vol:24, ISSN:1080-6040, Pages:258-266

Lynskey NN, Reglinski M, Calay D, et al., 2017, Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase, PLOS Pathogens, Vol:13, ISSN:1553-7366

Turner CE, Pyzio M, Song B, et al., 2016, Scarlet Fever Upsurge in England and Molecular-Genetic Analysis in North-West London, 2014, Emerging Infectious Diseases, Vol:22, ISSN:1080-6059

Reglinski M, Lynskey NN, Choi YJ, et al., 2016, Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG, Journal of Infection, Vol:72, ISSN:1532-2742, Pages:450-459

Turner CE, Lamagni T, Holden MT, et al., 2015, Turner et al. Reply to “Emergence of the Same Successful Clade among Distinct Populations of emm89 Streptococcus pyogenes in Multiple Geographic Regions”, Mbio, Vol:6, ISSN:2161-2129

Lynskey NN, Banerji S, johnson L, et al., 2015, Rapid lymphatic dissemination of encapsulated group A streptococci via lymphatic vessel endothelial receptor-1 interaction, PLOS Pathogens, Vol:11, ISSN:1553-7366

Moore LS, Leslie A, Meltzer M, et al., 2015, Corynebacterium ulcerans cutaneous diphtheria., The Lancet Infectious Diseases, Vol:15, ISSN:1474-4457, Pages:1100-1107

Turner CE, Abbott J, Lamagni T, et al., 2015, Emergence of a new highly successful acapsular group A Streptococcus clade of the genotype emm89 in the United Kingdom, Mbio, Vol:6, ISSN:2161-2129

Lamb LEM, Sriskandan S, Tan LKK, 2014, Bromine, bear-claw scratch fasciotomies, and the Eagle effect: management of group A streptococcal necrotising fasciitis and its association with trauma, The Lancet Infectious Diseases, Vol:15, ISSN:1474-4457, Pages:109-121

Lynskey NN, Goulding DA, Gierula M, et al., 2013, RocA truncation underpins hyper-encapsulation, carriage longevity and transmissibility of serotype M18 group A streptococci, Plos Pathogens, Vol:9, ISSN:1553-7374

Alam FM, Turner CE, Smith K, et al., 2013, Inactivation of the CovR/S Virulence Regulator Impairs Infection in an Improved Murine Model of Streptococcus pyogenes Naso-Pharyngeal Infection, PLOS One, Vol:8, ISSN:1932-6203

More Publications