Award details

A novel toxin delivery system in bacteria

Reference	BB/C008367/1
Principal Investigator / Supervisor	Dr Nicholas Waterfield
Co-Investigators / Co-Supervisors
Institution	University of Bath
Department	Biology and Biochemistry
Funding type	Research
Value (£)	244,471
Status	Completed
Type	Research Grant
Start date	21/11/2005
End date	20/08/2009
Duration	45 months

Abstract

Comparative genomics of insect and human pathogenic strains of the bioluminescent bacteria Photorhabdus, identified a novel class of mobile elements present in multiple copies in the genomes of both strains. These elements have been designated Photorhabdus Virulence Cassettes (PVC) as their 3'-ends usually encode homologues of known toxin genes. This region has been designated the payload region of the PVC. Supernatants of cosmid clones containing intact PVC elements alone were shown to be highly toxic to model insects when injected. Expression of selected payload toxins both in E. coli and also inside host cells suggests that they must gain access to the host cell cytoplasm to exert any toxic effect. This suggests that in addition to secretion from the bacterial cell that the PVC elements also mediate delivery into the host. Further, PVC elements appear to be derived from a mobile genetic element similar to bacteriophages and so they may also be responsible for their own horizontal transfer. We will: (1) Confirm that the payload proteins are the bona fide toxins responsible for the observed secreted toxic effect. (2) Determine the roles of the other PVC proteins in toxin secretion and delivery. (3) Determine how a given payload protein is targeted through the PVC system.

Summary

Pathogenic bacteria release toxins that effect host cells through a range of mechanisms called 'secretion systems'. Two well characterised secretion systems, called type III and type IV, have been previously described which allow bacteria to 'inject' toxins directly into the host cell using a 'molecular syringe'. We have identified a completely new toxin secretion system that allows a range of different toxins to be released from the bacteria and into host cells without this need for cell to cell contact. This system appears to be derived from a mobile genetic element similar to bacteriophages (viruses) and so may also be responsible for its own spread between different bacterial species.

Committee	Closed Committee - Plant & Microbial Sciences (PMS)
Research Topics	Microbiology
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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