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dc.contributor.advisorFitzgerald, Jonathanen
dc.contributor.advisorAit-Ali, Taharen
dc.contributor.authorBengtsson, Rebecca Jien
dc.date.accessioned2019-07-12T10:46:46Z
dc.date.available2019-07-12T10:46:46Z
dc.date.issued2019-06-29
dc.identifier.urihttp://hdl.handle.net/1842/35756
dc.description.abstractThe Gram-negative, obligate intracellular bacterium Lawsonia intracellularis is the aetiological agent of a non-zoonotic enteric disease known as proliferative enteropathy (PE). PE has been detected in wide range of mammalian species, including wild and domestic animals. The disease is most prevalent in pig herds where it is endemic, with both subclinical and clinical infections. Porcine PE was first described in 1931 and four different form of the disease are recognised, ranging from mild to severe clinical manifestations. Over recent years rising outbreaks of equine PE in foals have been reported and cross-species experimental infections have demonstrated host-specificity for infection. Although the dynamics of L. intracellularis infection have been examined, there is a lack of understanding population genetic structure and the basis for pathogenesis due to difficulties with culturing obligate intracellular organisms. In this study, we developed a pipeline to obtain high quality whole genome sequences of L. intracellularis through direct sequencing of clinical samples from field outbreaks of porcine and equine PE, and cell passaged samples without the requirement of cultivation, resulting in the generation of 25 draft genome assemblies. To explore the genetic diversity of L. intracellularis, we performed comparative analysis which revealed a clonal population structure among porcine derived isolates showing very limited diversity, indicative of emergence from a recent clonal expansion. Our analysis revealed that infections among different hosts are caused by genetically distinct L. intracellularis sub-types. Finally, we focussed on a core gene encoding a putative autotransporter, termed Lawsonia autotransporter B (latB), that exhibited genetic variation in different strains, and immunofluorescent staining for LatB revealed the putative autotransporter was expressed during infection and was associated with the bacterial outer membrane. Overall, these studies have provided insights into the genetic diversity and evolutionary origin of L. intracellularis, enhancing our understanding of the population biology of this important animal pathogen.en
dc.contributor.sponsorBiotechnology and Biological Sciences Research Council (BBSRC)en
dc.language.isoen
dc.publisherThe University of Edinburghen
dc.relation.hasversionBENGTSSON, R. J., MACINTYRE, N., GUTHRIE, J., WILSON, A. D., FINLAYSON, H., MATIKA, O., PONG-WONG, R., SMITH, S. H., ARCHIBALD, A. L. & AIT-ALI, T. 2015. Lawsonia intracellularis infection of intestinal crypt cells is associated with specific depletion of secreted MUC2 in goblet cells. Veterinary Immunology andIimmunopathology, 168, 61-67.en
dc.relation.hasversionHUAN, Y. W., BENGTSSON, R. J., MACINTYRE, N., GUTHRIE, J., FINLAYSON, H., SMITH, S. H., ARCHIBALD, A. L. & AIT-ALI, T. 2017. Lawsonia intracellularis exploits β- catenin/Wnt and Notch signalling pathways during infection of intestinal crypt to alter cell homeostasis and promote cell proliferation. PloS one, 12, e0173782.en
dc.subjectLawsonia intracellularisen
dc.subjectproliferative enteropathyen
dc.subjectlow levels of genetic diversityen
dc.titlePopulation and functional genomic analysis of Lawsonia intracellularisen
dc.typeThesis or Dissertationen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD Doctor of Philosophyen


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