Contact details
Professor Shiranee Sriskandan
Professor of Infectious Diseases
Department of Medicine
Hammersmith Hospital
Hammersmith Campus
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Professor Shiranee Sriskandan
Gram Positive Molecular Pathogenesis
Streptococcus pyogenes forming chains of adherent Gram positive cocci
Our research addresses the potential mechanisms by which serious Gram positive pathogens cause disease, using, as a paradigm of this type of infection, the group A streptococcus (Streptococcus pyogenes). S pyogenes causes a spectrum of disease ranging from pharyngitis to necrotising fasciitis and toxic shock. It is also responsible for post-streptococcal rheumatic fever, the leading cause of acquired valvular heart disease in the developing world.
Research projects also include the important pathogens Staphylococcus aureus and Clostridium difficile. Their study forms the laboratory-based research programme of the UKCRC-funded Centre for Infection Prevention and Management.
The group also works closely with honorary Lecturer, Dr Siouxsie Wiles , who has a strong interest in bioluminescent imaging. Our research examines the interface between pathogen molecular microbiology and host immune response, and builds on our considerable clinical experience of severe bacterial sepsi.
Puerperal sepsis isolates from 1934 associated with outbreaks of lethal infection
A focus of our work is the role of bacterial superantigens in the molecular pathogenesis of both experimental and clinical sepsis. The laboratory has developed a number of streptococcal mutants which do not express superantigens, for example, the classical phage-encoded scarlet fever toxin, SPEA (streptococcal pyrogenic exotoxin A) and the intriguingly potent chromosomal superantigen SMEZ (streptococcal mitogenic exotoxin Z). There is also considerable interest in the staphylococcal superantigen toxins that cause both menstrual and non-menstrual toxic shock. Evasion of the human innate immune response is a key feature of these pathogens and the group has a keen interest in the function and regulation of the streptococcal CXC chemokine-cleaving protease, SpyCEP (Streptococcus pyogenes cell envelope protease, cepA) as well as regulation of bacterial capsule production. Publications from the group can be found using by clicking here
Ongoing projects include:
- The role of superantigenic toxins such as SPEA,SMEZ , SEB, SEC in bacterial pathogenesis using a superantigen-sensitive HLA class II transgenic system
- Efficacy of intravenous immunoglobulin and impact of antimicrobial treatment on toxin production during serious streptococcal and staphylococcal infection
- Mechanisms by which the protease SpyCEP prevents neutrophil accumulation at sites of infection through cleavage of key human chemokines
- Vaccine potential of SpyCEP
- Epidemiology and molecular pathogenesis of postpartum streptococcal sepsis comparing outbreaks in 1930s with contemporary outbreaks
- Capsule regulation in hypermucoid strains
- Bioluminescent Staphylococus aureus and Streptococcus pyogenes strains
- Modelling nasopharyngeal carriage of bacteria
- Identification of novel pathogenetic markers of highly virulent Staphylococcus aureus and Clostridium difficile strains
Necrotising fasciitits: Left image, neutrophils marginating in blood vessels at site of necrotising infection caused by S pyogenes. Despite abundant bacterial growth (arrowed), neutrophils are not present in the infected tissues. Right image, the chemokine interluekin-8/CXCL8 demonstrating cleavage following exposure to the protease SpyCEP.
Collaborations
In addition to the new Centre for Infection Preventions and Management, we have longstanding collaborations with our colleagues Dr Robert Edwards (Experimental Medicine) and Professor Danny Altmann (Infectious Diseases & Immunity) . Increasingly, we collaborate with the Centre for Infections, HPA, Colindale and colleagues in the Diagnostic Microbiology service (Dr Kathy Bamford). New projects are developing in collaboration with Dr James Pease (Leukocyte Biology), Dr Angelika Grundling (Microbiology), and, through CIPM, with Professors Neil Fairweather and Mark Enright.
