Microbiology and Infection Unit
Division of Translational and Systems Medicine
Seminar Series 2014/2015
Genetic analysis of Salmonella
and E. coli pathogenesis
Professor Mark Stevens
Chair of Microbial Pathogenesis and Research Director
The Roslin Institute and Royal (Dick) School of Veterinary Studies
University of Edinburgh
Abstract:
Salmonella enterica and enterohaemorrhagic Escherichia coli are zoonotic bacterial pathogens of
worldwide importance. Human infections are often acquired via the food chain or environment from
farmed animals and involve acute enteritis that can be complicated by life-threatening sequelae. Toward
the design of strategies to control such pathogens in reservoir hosts, we have sought to identify bacterial
genes mediating persistence and pathogenesis in farmed animals. Most recently this has involved the use
of transposon-directed insertion-site sequencing (TraDIS) to assign roles to thousands of S. Typhimurium
and E. coli O157:H7 genes in intestinal colonisation of farmed animals. TraDIS relies on massivelyparallel sequencing of transposon flanking regions and allows both the identity and phenotype of
hundreds of random mutants to be simultaneously assigned following screening of complex pools of
mutants in animals. The mode of action of selected virulence factors has been characterised and vaccines
or inhibitors targeting them evaluated. We have used similar methods together with novel surgical
models to unravel why some S. enterica serovars differ in virulence and tissue tropism in cattle,
providing novel data on the basis of systemic translocation of Salmonella that challenge received wisdom
from murine typhoid models. My talk will explore what we have learned about the basis of virulence of
Salmonella and E. coli O157:H7 as well as approaches to reduce animal use in the study of microbial
disease.
Biography:
Dr Stevens’ laboratory studies Salmonella, Campylobacter and E. coli infections in foodproducing animals, with emphasis on the role of bacterial and host factors in
persistence, pathogenesis and protection. In recent years, he has used high-density
mutagenesis to assign roles to thousands of Salmonella and E. coli genes during
infection of farmed animals, as well as novel surgical models to understand how some
serovars and pathotypes migrate from mucosal surfaces to cause systemic disease.
These approaches have provided rich annotation of the function of bacterial genes in
relevant hosts and informed the design of vaccines and other control strategies. He has
also sought to unravel the basis of heritable resistance of chickens to Salmonella and Campylobacter,
including via genome-wide association studies to map resistance-associated loci and understand how
they exert their effect. He holds a first class degree in Microbiology & Virology from the University of
Warwick, a PhD on regulation of virulence genes in meningitis-associated E. coli and worked for 12 years
at the Institute for Animal Health before joining The Roslin Institute in 2011.
7 October 2015
@ 12.00pm-1.00pm, Microbial Bioinformatics Unit (MBU),
Microbiology and Infection Unit, Warwick Medical School,
Medical School Building, University of Warwick
For queries please contact Jas Bains
Email: j.k.bains@warwick.ac.uk
Tel: 024 7657 5669