title: From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity.
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.
authors.affiliation: School of Biological Sciences, University of Reading, Whiteknights, Reading, RG6 6AJ, United Kingdom.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Mulley
authors.affiliation: Cardiff School of Health Sciences, Cardiff Metropolitan University, Llandaff Campus, Western Avenue, Cardiff, CF5 2YB, United Kingdom.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Beeton
authors.affiliation: Life Sciences Building, Bristol University, 24 Tyndall Avenue, Bristol, BS8 1TQ, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Wilkinson
authors.affiliation: Life Sciences Building, Bristol University, 24 Tyndall Avenue, Bristol, BS8 1TQ, United Kingdom.
authors.forename: Isabella
authors.initials: I
authors.lastname: Vlisidou
authors.affiliation: Primary Care Unit, Microbiology Department, Public Health England, Gloucester Royal Hospital, Great Western Road, Gloucester, GL1 3NN, United Kingdom.
authors.forename: Nina
authors.initials: N
authors.lastname: Ockendon-Powell
authors.affiliation: Division of Biomedical Sciences, Warwick Medical School, Medical School Building, The University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, United Kingdom.
authors.forename: Alexia
authors.initials: A
authors.lastname: Hapeshi
authors.affiliation: Buchmann Center for Life Sciences (BMLS), Fachbereich Biowissenschaften, Goethe Universität Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Tobias
authors.affiliation: Buchmann Center for Life Sciences (BMLS), Fachbereich Biowissenschaften, Goethe Universität Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Friederike I
authors.initials: FI
authors.lastname: Nollmann
authors.affiliation: Buchmann Center for Life Sciences (BMLS), Fachbereich Biowissenschaften, Goethe Universität Frankfurt, 60438, Frankfurt, Germany.
authors.forename: Helge B
authors.initials: HB
authors.lastname: Bode
authors.affiliation: Department of Biology & Biochemistry, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom.
authors.forename: Jean
authors.initials: J
authors.lastname: van den Elsen
authors.affiliation: Biosciences, Cornwall Campus, University of Exeter, Penryn, TR10 9EZ, United Kingdom.
authors.forename: Richard H
authors.initials: RH
authors.lastname: ffrench-Constant
authors.affiliation: Division of Biomedical Sciences, Warwick Medical School, Medical School Building, The University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, United Kingdom.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Waterfield
mesh_terms: D000818:Animals; D018441:Biofilms; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D006801:Humans; D018402:Manduca / Q000382:microbiology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020637:Photorhabdus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D012329:RNA, Bacterial / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013696:Temperature
chemical_list: D012329:RNA, Bacterial