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Abstract
The Toxin Complex (TC) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus, but now seen in a range of pathogens, including those of humans. These complexes comprise three protein subunits, A, B and C which in the Xenorhabdus toxin are found in a 4:1:1 stoichiometry. Some TCs have been demonstrated to exhibit oral toxicity to insects and have the potential to be developed as a pest control technology. The lack of recognisable signal sequences in the three large component proteins hinders an understanding of their mode of secretion. Nevertheless, we have shown the Photorhabdus luminescens (Pl) Tcd complex has been shown to associate with the bacteria's surface, although some strains can also release it into the surrounding milieu. The large number of tc gene homologues in Pl make study of the export process difficult and as such we have developed and validated a heterologous Escherichia coli expression model to study the release of these important toxins. In addition to this model, we have used comparative genomics between a strain that releases high levels of Tcd into the supernatant and one that retains the toxin on its surface, to identify a protein responsible for enhancing secretion and release of these toxins. This protein is a putative lipase (Pdl1) which is regulated by a small tightly linked antagonist protein (Orf53). The identification of homologues of these in other bacteria, linked to other virulence factor operons, such as type VI secretion systems, suggests that these genes represent a general and widespread mechanism for enhancing toxin release in Gram negative pathogens.
Original language | English |
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Article number | e1002692 |
Number of pages | 12 |
Journal | PLoS Pathogens |
Volume | 8 |
Issue number | 5 |
DOIs | |
Publication status | Published - 17 May 2012 |
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- 2 Finished
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RAPID BACTERIAL VIRULENCE ANNOTATION FOR THE POST GENOMIC ER A
Waterfield, N. (PI)
Biotechnology and Biological Sciences Research Council
1/07/07 → 30/09/10
Project: Research council
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A NOVEL TOXIN DELIVERY SYSTEM IN BACTERIA
Waterfield, N. (PI)
Biotechnology and Biological Sciences Research Council
21/11/05 → 6/08/09
Project: Research council