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 Group

Based in the Section of Adult Infectious Disease, my group is 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)Our work focusses on Streptococcus pyogenes the bacterium that causes tonsillitis and scarlet fever, but also 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.

Research is in the group is mainly driven by unexpected changes we see in either the bacteria, patient disease phenotype, or disease epidemiology. This has led to  work on novel proteases that cleave chemokines, that might function as vaccine targets, as well as unexpected routes of bacterial dissemination in the lymphatic system.  It is also clear that both large and small scale genome remodelling in S. pyogenes can have major impacts on disease frequency; in the last decade, the UK has seen new sublineages of serotypes M89 and M1 emerge and expand to account for increasing proportions of invasive infections. 

S. pyogenes transmission in classThe main reservoir of S. pyogenes is the throat. One long-standing interest is the impact that the classical phage-encoded scarlet fever toxins like SPEA play in perpetuating outbreaks of scarlet fever and pharyngitis in children in schools, as well as their potential to trigger superantigen-mediated toxic shock during invasive infection. 

Cleavage of CXCL8 by SpyCEP

Evasion of the innate immune response is a trademark of S. pyogenes and we have focussed on the CXC-chemokine cleaving protease SpyCEP (cepA) and the homologue C5a peptidase (scpA) that cleaves C3a and C5a. Proteases like these, that are conserved, demonstrate that repulsion of the neutrophil response is central to S. pyogenes pathogenesis and highlight their potential as 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

The group's research tries to understand trends in streptococcal and other bacterial diseases, to help inform interventions that might improve public health. As theme lead for ‘Priority Pathogens’ in the NIHR Health Protection Research Unit (HPRU) in Healthcare Associated Infection and Antimicrobial Resistance,  we have been examining the molecular basis for bacterial infections relevant to healthcare settings, such as Escherichia coli bacteremia, antimicrobial resistance, and, of course, haemolytic streptococcal infections.  Many of these projects are in partnership with UKHSA (the UK Health Security Agency, formerly Public Health England). 

Much of our work recently has been influenced by the COVID-19 pandemic; where possible patient-focussed studies and even our schools transmission research have been adapted to help identify biomarkers of infection and routes of SARS-CoV2 transmission. We are fortunate to be supported by our colleagues in clinical infection and the new BRC-supported Colebrook AMR laboratory that supports clinical and microbial biobanking.

CURRENT PROJECTS


  • SpyCEP and C5a peptidase - Wellcome Trust Collaborative grant with Steven Matthews (CMBI/Life Sciences) and James Pease (NHLI)
  • Molecular anatomy of S. pyogenes and scarlet fever  in UK (MRC project in collaboration with UKHSA)
  • Schools Transmission Studies (Action Medical Research and UKRI, in collaboration with UKHSA)
  • 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 and others) - ongoing biomarker projects using RNAseq, metabonomics, cytokines. 
  • Molecular basis for upsurge in E. coli bacteremia, genomics, nitrofurantoin resistance (HPRU collaboration with UKHSA)
  • AMRWATCH- NERC-funded project to understand the impact of antimicrobial manufacturing on AMR in India with partners in Centre for Environmental Policy (CEP, Nick Voulvoulis) and India 
  • The Colebrooks and the history of antimicrobial treatment of S. pyogenes (see Research tab)

Selected Publications

Journal Articles

Cordery R, Purba AK, Begum L, et al., 2022, Frequency of transmission, asymptomatic shedding, and airborne spread of Streptococcus pyogenes in schoolchildren exposed to scarlet fever: a prospective, longitudinal, multicohort, molecular epidemiological, contact-tracing study in England, UK., Lancet Microbe, Vol:3, Pages:e366-e375

Mehta R, Chekmeneva E, Jackson H, et al., 2022, Antiviral metabolite 3’-Deoxy-3’,4’-didehydro-cytidine is detectable in serum and identifies acute viral infections including COVID-19, Med, Vol:3, ISSN:2666-6340, Pages:204-215.e6

Li HK, Kaforou M, Rodriguez-Manzano J, et al., 2021, Discovery and validation of a 3-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations; a case-control then observational cohort study, The Lancet Microbe, Vol:2, ISSN:2666-5247, Pages:594-603

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

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, 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

More Publications