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Title: Genetic dissection of Anopheles gambiae epithelial responses to gut commensal bacteria
Author: Stathopoulos, Stavros
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2013
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Commensal bacteria inhabiting the mosquito gut have been shown to profoundly influence the outcome of infection with malaria Plasmodium parasites. Genetic variation within mosquito populations has also been associated with the outcome of Plasmodium infections, especially with regard to immune factors, many of them targeting both bacteria and Plasmodium parasites. Although bacteria are considered a major evolutionary force that may affect survival, no link has yet to emerge between mosquito genetic variation and the outcome of bacterial infections. To test this possibility, a model of oral infections was established in Anopheles gambiae, the major malaria vector, with two common members of the mosquito gut microbiota, Asaia and Serratia marcescens. Using genome-wide SNP genotyping and expression analyses, mosquito genes associated with the outcome of Serratia infection and differentially expressed following Asaia or Serratia infection were identified. Three genes encoding type III fibronectin domains (FN3D1-3), associated with the outcome of Serratia infection, were shown to limit Serratia abundance and shift the mosquito gut bacterial population structure by limiting mainly Enterobacteriaceae, suggesting that mosquito responses shape the gut bacterial community with much higher specificity than previously thought. Furthermore, silencing of the gene encoding the gustatory receptor Gr9, also associated with the Serratia infection outcome, was shown to radically increase Serratia levels following oral infection, in a behavioural response than mostly relied on changes in neuropeptide F expression. Both the expression and SNP genotyping analysis indicated the existence of an epithelial and a behavioural mode of immunity following oral bacterial infection and revealed the complexity and specificity of this intricate biological system that is expected to shape malaria transmission dynamics.
Supervisor: Christophides, George Sponsor: Wellcome Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available