Differential Spatial Repositioning of Activated Genes in Biomphalaria glabrata Snails Infected with Schistosoma mansoni

Autor: Arican-Goktas, HD, Ittiprasert, W, Bridger, JM, Knight, M
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS Neglected Tropical Diseases
PLoS Neglected Tropical Diseases, Vol 8, Iss 9, p e3013 (2014)
ISSN: 1935-2735
1935-2727
Popis: Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.
Author Summary Bilharzia is a parasitic disease endemic in many parts of the world. The schistosoma parasite that causes Bilharzia infects humans but uses a fresh water snail as a secondary host. These two organisms have co-evolved together, and as such the parasite will have mechanisms to overcome the host defences. Understanding this delicately balanced relationship is fundamental to controlling or eradicating the disease. We have studied how this parasite can influence how the DNA within the snail behaves. We have shown snail genes have specific locations within the cell nuclei. Further, we have revealed that specific snail genes related to a schistosome infection change to a new non-random nuclear location as they are turned on or up-regulated. We have snail strains that are susceptible or resistant to the infection of parasites and we can also take live parasites and make them unable to complete an infection by irradiating them. In this unique study, we have shown a gene that is involved in stress pathways moves to a new nuclear location and becomes turned on, but only in susceptible snails, infected with fully functional parasite. Our data suggest that this gene is regulated by the parasite, which has control over the host's DNA, so that the gene is moved to an area where it can be actively expressed. We have uncovered a novel mechanism whereby the spatial organization of a host organism is interfered with by a pathogen. This type of control is probably found in other host-pathogen relationships.
Databáze: OpenAIRE
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