MOLECULAR PATHOGENESIS GRAM-NEGATIVE BACTERIAL PATHOGENS AND AMR
We have several intertwined research streams:
EPEC AND EHEC PATHOGENESIS AND HOST RESPONSES
We investigate infections with enterohaemorrhagic Escherichia coli (EHEC), which causes haemorrhagic colitis and haemolytic uraemic syndrome (HUS), and enteropathogenic E. coli (EPEC), which causes paediatric diarrhoea mainly in low and middle-income countries. EPEC and EHEC employ a type III secretion system (T3SS) to inject dozens of effectors that take control of cell signaling (1,2). We study the structure and function of the effectors (for example 3,4).
Mice are inherently resistant to EPEC and EHEC infection. For this reason we extensively make use of the related mouse pathogen Citrobacter rodentium, which shares an infection strategy and effectors with EPEC and EHEC (5,6). In particular, we investigate the impact of C. rodentium infection on infected intestinal epithelial cells (IECs) in vivo using isobaric labelling proteomics, targeted metabolomics and lipidomics. We also study the impact of C. rodentium infection on the composition of faecal and mucosal associated gut microbiota.
EHEC, EPEC and C. rodentium colonise the gut mucosa via formation of attaching and effacing lesions.
Infections with Salmonella Typhi belonging to haplotype H58
Salmonella enterica serovar Typhi (S. Typhi) cause the systemic disease, typhoid fever. Its virulence depends on the activity of two T3SSs carried on Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2), which secrete a pool of over 40 effectors to subvert host cell processes to permit immune evasion, invasion, and intracellular growth. The need to better understand S. Typhi infection has been intensified by the recent spread of haplotype 58 (H58), also known as 4.3.1, that has clonally expanded worldwide to become the dominant cause of multi-drug resistant (MDR) typhoid across South and Southeast Asia and East Africa. We are aiming to understand the reasons underlying the relative success of H58 strains (7).
Professor Gad Frankel
Gad Frankel obtained his B.Sc. in Biology and subsequently his Ph.D in Genetics from the Hebrew University of Jerusalem. He has held a Howard Hughes Fellowship in the Department Microbiology and Immunology, Stanford University, CA, USA. Following a short stay at the Weizmann Institute in Rehovot, he was appointed a research fellow at Imperial College. In 1998 he was appointed Lecturer at Imperial College, was promoted to Reader in 2000 and to Professor in 2002. He is currently Professor of Bacterial Pathogenesis at the Department of Life Sciences and the MRC Centre for Molecular Bacteriology and Infection (CMBI) at Imperial College London.
|Dr Rachael Barry||Dr Cedric Berger||Dr Valerie Crepin||Dr Olga Kotik|
|Dr Carrie Mullineaux-Sanders||Dr David Ruano-Gallego||Dr Ernest So|
|Ms Danielle Carson||Ms Pippa Goddard||Ms Rebecca Johnson|
et al., 2013, A type III effector antagonizes death receptor signalling during bacterial gut infection, Nature, Vol:501, ISSN:0028-0836, Pages:247-+
et al., 2012, EspZ of Enteropathogenic and Enterohemorrhagic Escherichia coli Regulates Type III Secretion System Protein Translocation, MBIO, Vol:3, ISSN:2150-7511