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From insect to man : photorhabdus sheds light on the emergence of human pathogenicity
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Mulley, Geraldine, Beeton, Michael L., Wilkinson, Paul, Vlisidou, Isabella, Ockendon-Powell, Nina, Hapeshi, Alexia , Tobias, Nick J., Nollmann, Friederike I., Bode, Helge B., van den Elsen, Jean, ffrench-Constant, Richard H. and Waterfield, Nicholas R. (2015) From insect to man : photorhabdus sheds light on the emergence of human pathogenicity. PLoS One, 10 (12). e0144937. doi:10.1371/journal.pone.0144937
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Official URL: http://dx.doi.org/10.1371/journal.pone.0144937
Abstract
Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | R Medicine > RB Pathology | ||||||||
| Divisions: | Faculty of Medicine > Warwick Medical School | ||||||||
| Library of Congress Subject Headings (LCSH): | Pathogenic bacteria, Heterorhabditidae, Vector-pathogen relationships , Insects -- Diseases | ||||||||
| Journal or Publication Title: | PLoS One | ||||||||
| Publisher: | Public Library of Science | ||||||||
| ISSN: | 1932-6203 | ||||||||
| Official Date: | 17 December 2015 | ||||||||
| Dates: |
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| Date of first compliant deposit: | 21 December 2015 | ||||||||
| Volume: | 10 | ||||||||
| Number: | 12 | ||||||||
| Article Number: | e0144937 | ||||||||
| DOI: | 10.1371/journal.pone.0144937 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Seventh Framework Programme (European Commission) (FP7) | ||||||||
| Grant number: | (BBE0213281), grant EMBEK1 (number 211436), grant GAMEXP (number 223328), |
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