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 ISSN 1932-6203.

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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 Science, Engineering and Medicine > 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:	Date Event 17 December 2015 Published 25 November 2015 Accepted 1 October 2015 Submitted
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 (Creative Commons)
Date of first compliant deposit:	21 December 2015
Date of first compliant Open Access:	21 December 2015
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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