TY  - JOUR
A1  - Mulley, Geraldine
A1  - Beeton, Michael L.
A1  - Wilkinson, Paul
A1  - Vlisidou, Isabella
A1  - Ockendon-Powell, Nina
A1  - Hapeshi, Alexia
A1  - Tobias, Nicholas J.
A1  - Nollmann, Friederike I.
A1  - Bode, Helge Björn
A1  - Elsen, Jean van den
A1  - ffrench-Constant, Richard H.
A1  - Waterfield, Nicholas R.
T1  - From insect to man : Photorhabdus sheds light on the emergence of human pathogenicity
T2  - PLoS one
N2  - 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.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/39038
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-390385
SN  - 1932-6203
N1  - Copyright: © 2015 Mulley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
VL  - 10
IS  - (12): e0144937
SP  - 1
EP  - 32
PB  - PLoS
CY  - Lawrence, Kan.
ER  -