From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity.
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 poikil...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0144937 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850125253790924800 |
|---|---|
| author | Geraldine Mulley Michael L 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 |
| author_facet | Geraldine Mulley Michael L 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 |
| author_sort | Geraldine Mulley |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0746e423c2f84ea1b19def4b054f7fa6 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-0746e423c2f84ea1b19def4b054f7fa62025-08-20T02:34:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-011012e014493710.1371/journal.pone.0144937From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity.Geraldine MulleyMichael L BeetonPaul WilkinsonIsabella VlisidouNina Ockendon-PowellAlexia HapeshiNick J TobiasFriederike I NollmannHelge B BodeJean van den ElsenRichard H ffrench-ConstantNicholas R WaterfieldPhotorhabdus 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.https://doi.org/10.1371/journal.pone.0144937 |
| spellingShingle | Geraldine Mulley Michael L 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 From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. PLoS ONE |
| title | From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. |
| title_full | From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. |
| title_fullStr | From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. |
| title_full_unstemmed | From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. |
| title_short | From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity. |
| title_sort | from insect to man photorhabdus sheds light on the emergence of human pathogenicity |
| url | https://doi.org/10.1371/journal.pone.0144937 |
| work_keys_str_mv | AT geraldinemulley frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT michaellbeeton frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT paulwilkinson frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT isabellavlisidou frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT ninaockendonpowell frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT alexiahapeshi frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT nickjtobias frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT friederikeinollmann frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT helgebbode frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT jeanvandenelsen frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT richardhffrenchconstant frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity AT nicholasrwaterfield frominsecttomanphotorhabdusshedslightontheemergenceofhumanpathogenicity |