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From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

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posted on 20.05.2022, 14:22 authored by Geraldine Mulley, Mike BeetonMike Beeton, Paul Wilkinson, Isabella Vlisidou, Nina Ockendon-Powell, Alexia Hapeshi, Nick J. Tobias, Friederike I. Nollmann, Helge B. Bode, Jean van den Elsen, Richard H. ffrench-Constant, Nicholas R. Waterfield

 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. 

Funding

This work was supported by the BBSRC (grant number BBE0213281), EU FP7 consortium grant EMBEK1 (number 211436), EU FP7 consortium grant GAMEXP (number 223328), and Warwick University Medical School

History

Published in

PLOS One

Publisher

PLOS

Version

VoR (Version of Record)

Citation

Mulley G., Beeton M.L., Wilkinson P., Vlisidou I., Ockendon-Powell, N., Hapeshi, A., Tobias, N.J., Nollmann, F.I., Bode, H.B., van den Elsen, J., ffrenc-Constant, R.H. & Waterfield, N.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

Electronic ISSN

1932-6203

Cardiff Met Affiliation

Cardiff School of Sport and Health Sciences

Cardiff Met Authors

Michael Beeton

Cardiff Met Research Centre/Group

  • Microbiology & Infection

Copyright Holder

© The Authors

Language

en

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