ProfessorShiraneeSriskandan

Summary

Gram Positive Pathogenesis Group

Based in the Section of Adult Infectious Disease, my group is part of Imperial's Centre for Bacterial Resistance Biology (CBRB) and the NIHR Health Protection Research Unit (HPRU) in Healthcare Associated Infection and Antimicrobial Resistance.

My 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. 

The 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. 

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 (CBRB/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 transmission (MRC project with David Green, SPH, Imperial and 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 (Professor Joseph Selvin and team)
• The Colebrooks and the history of antimicrobial treatment of S. pyogenes (see Research tab)

Selected Publications

Journal Articles

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