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.
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.
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.
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
- 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)
- 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)
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., 2017, Multi-functional mechanisms of immune evasion by the streptococcal complement inhibitor C5a peptidase, PLOS Pathogens, Vol:13, ISSN:1553-7366
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
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, 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
et al., Rapid lymphatic dissemination of encapsulated group A streptococci via lymphatic vessel endothelial receptor-1 interaction, PLOS Pathogens, Vol:11, ISSN:1553-7366
et al., 2015, Corynebacterium ulcerans cutaneous diphtheria., The Lancet Infectious Diseases, Vol:15, ISSN:1474-4457, Pages:1100-1107
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
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
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