Salmonella enterica

Targeted and genome-wide mutagenesis is being used to identify Salmonella genes required for intestinal colonisation of chickens, pigs and cattle. Our recent data indicates that different factors are deployed to colonise different hosts [2], and ongoing projects aim to assign roles to each transposable gene during infection and dissect their mode of action. The molecular basis of Salmonella-induced enteritis and of systemic translocation of host-restricted serovars in livestock is also being elucidated using novel surgical models. The fate of S. enterica serovars following invasion of the intestines is also under study [ Fig. 1].

Campylobacter jejuni

Current collaborative projects on Campylobacter [ Fig. 2] aim to understand bacterial population dynamics during colonisation and transmission in chickens, define the functional relevance of flagellin glycosylation and iron uptake systems, as well as to evaluate the efficacy and mode of action of live-attenuated vaccines presenting Campylobacter antigens. The Institute also researches the genetic and immunological basis of protection against Campylobacter using inbred chicken lines exhibiting heritable differences in resistance .

Enterohaemorrhagic Escherichia coli (EHEC)

Mutagenesis of E. coli O157:H7 and of non-O157 EHEC has identified portfolios of bacterial genes required for intestinal colonisation of cattle, including conserved and serogroup-specific factors [3], some of which have been evaluated as subunit vaccines. Ongoing research focuses on the role of proteins injected into enterocytes via a Type III secretion system [Fig. 3], some of which subvert actin dynamics [4], and the structure, function and role in virulence of EHEC cytotoxins.

Our research also established that the host stress hormone norepinephrine (NE) augments EHEC-induced enteritis and adherence in the bovine intestines [5], providing a potential molecular link between stress and susceptibility to microbial infection. Ongoing projects aim to define the impact of host and dietary neurochemicals on the outcome of Salmonella and EHEC infections in livestock and the mechanisms of hormone sensing and signal transduction.

Avian pathogenic Escherichia coli (APEC)

APEC cause colibacillosis, a severe and recalcitrant disease of poultry associated with spread of the bacteria from mucosal surfaces to the visceral organs. Though not considered a threat to food safety, APEC are a major cause of production losses and threaten the security of food supply. With joint funding from the BBSRC and British Poultry Council we are identifying bacterial genes influencing the carriage and virulence of APEC in turkeys and conducting research to understand and rationally improve the protection conferred by existing vaccines.

Burkholderia pseudomallei

B. pseudomallei causes a glanders-like disease in animals and humans. Though not an enteric pathogen we have established that it uses strategies in common with Shigella to enter cells, escape the entry vesicle and promote its motility within cells by subverting cellular actin dynamics. Ongoing BBSRC funded research aims to unravel the molecular mechanisms underlying these processes.

References:

  • Stevens MP, Stevens JM, Jeng RL, Taylor LA, Wood MW, Hawes P, Monaghan P, Welch MD, Galyov EE. (2005) Identification of a bacterial factor required for actin-based motility of Burkholderia pseudomallei. Molecular Microbiology 56:40-53[Abstract]
  • Morgan E, Campbell JD, Rowe SC, Bispham J, Stevens MP, Bowen AJ, Barrow PA, Maskell DJ, Wallis TS. (2004) Identification of host-specific colonization factors of Salmonella enterica serovar Typhimurium. Molecular Microbiology 54:994-1010. [Abstract].
  • van Diemen PM, Dziva F, Stevens MP, Wallis TS. (2005) Identification of enterohemorrhagic Escherichia coli O26:H- genes required for intestinal colonization in calves. Infection & Immunity 73:1735-43. [Abstract].
  • Stevens JM, Galyov EE, Stevens MP. (2006) Actin-dependent movement of bacterial pathogens. Nature Reviews Microbiology 4:91-101. [Abstract]
  • Vlisidou I, Lyte M, van Diemen PM, Hawes P, Monaghan P, Wallis TS, Stevens MP. (2004) The neuroendocrine stress hormone norepinephrine augments Escherichia coli O157:H7-induced enteritis and adherence in a bovine ligated ileal loop model of infection. Infection & Immunity 72:5446-51. [Abstract].