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.
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.
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
- 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)
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
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
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
et al., 2020, Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection, Nature Communications, Vol:11, ISSN:2041-1723
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
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
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