Exploring host response to bacterial infection

Yi Xin Ye (2010). Exploring host response to bacterial infection PhD Thesis, School of Biological Sciences, The University of Queensland.

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Author Yi Xin Ye
Thesis Title Exploring host response to bacterial infection
School, Centre or Institute School of Biological Sciences
Institution The University of Queensland
Publication date 2010-03
Thesis type PhD Thesis
Supervisor Elizabeth McGraw
Stephen Chenoweth
Total pages 151
Total black and white pages 151
Subjects 06 Biological Sciences
Abstract/Summary Much of our current mechanistic understanding of the innate immune response in animals has grown out of empirical work in insect models, especially the fruit fly Drosophila melanogaster. The mainstream understanding of the fly immune response to bacteria has been that it exists in two parts; a cellular and a humoral response. Drosophila also harbor substantial genetic variation for antibacterial defense and investment in immunity is thought to involve a costly trade-off with life history traits, including development, life-span and reproduction. My first study (chapter 2) aimed to understand the way in which insects invest in fighting bacterial infection. We selected for survival following systemic infection with the opportunistic pathogen, Pseudomonas aeruginosa in wild-caught D. melanogaster over 10 generations. We then examined genome wide changes in expression in the selected flies relative to unselected controls, both of which had been infected with the pathogen to specifically identify the genetic basis of the evolved immune response. In response to selection, population level survivorship to infection increased from 15% to 70%. The evolved capacity for defense was costly as evidenced by reduced longevity and larval viability and a rapid loss of the trait once selection pressure was removed. Counter to expectation, we observed more rapid developmental rates in the selected flies. Selection associated changes in expression of genes with dual involvement in developmental and immune pathways suggest pleiotropy as a possible mechanism for the positive correlation. We also found that both the Toll and Imd pathways work synergistically to limit infectivity and that cellular immunity plays a more critical role in overcoming P. aeruginosa infection than previously reported. Females usually produce a more robust immune response and are often less susceptible to infection. This female bias has been documented in humans, mice and some birds and reptiles. The most common explanation is that males increase their mating success at the cost of immune investment whilst females invest in immunity to maximize life-time egg production. In insects, however, there is growing evidence of male-biased immune performance. Using fly survival data from my first study, I found that males exhibited higher post-infection survival than females. In my second study (chapter 3), I related these differences in survival rate to changes in gene transcription. Firstly, we examined the expression of a set of immunity genes in both sexes in the presence and absence of infection. We found that male-biased survival may be partially attributable to a higher baseline expression of immune genes in males. Contrary to previous published work, we found that immune gene expression was readily induced in flies upon exposure to P. aeruginosa and that the two sexes responded in a similar manner. Lastly, we found that selection altered the expression of genes in males alone and only in the presence of infection. Together our findings suggest a superior immune response in male Drosophila. Wolbachia pipientis is an obligate intracellular bacterium capable of spreading itself through populations by manipulating the reproduction of its hosts. The Wolbachia strain wMelPop, which reduces longevity in D. melanogaster, has been introduced into the Dengue virus mosquito vector, Aedes aegypti, as a strategy to reduce disease transmission. The infecting Wolbachia halve the lifespan of the mosquito and induce numerous behavioral and physiological abnormalities including heightened locomotor activity and an age dependent reduction in blood feeding success. In my third study (chapter 4), we aimed to understand the mechanism underpinning these changes and hence chose to explore how Wolbachia may be interacting with the insect’s nervous and muscle tissue. Because wMelPop over-replicates in Drosophila, first we measured the bacterial density in A. aegypti. We found that there was a relationship between some of the feeding associated defects in the mosquito and the density of Wolbachia in the nervous and muscle tissue. Next, we carried out a series whole genome profiling experiments based on the head and muscle tissues to identify mosquito pathways affected by the microbe. Key findings that may relate to the phenotypes of interest include increased expression of genes relating to muscle contraction and synthesis of the neurotransmitter dopamine. Other novel findings that may not relate directly to the phenotypes of interest include evidence of a strong local tissue based immune response and widespread changes in expression of mosquito methylation and acetylation associated genes. We then used then amplification of inter-methylated sites (AIMS test) to obtain DNA fingerprints representative of the methylome of A. aegypti infected and uninfected with wMelPop. The presence of wMelPop caused hypermethylation in loci where they were not methylated in uninfected mosquitoes.
Keyword Drosophila, Aedes, Pseudomonas, Wolbachia, innate immunity, host-pathogen interaction, evolution, selection, gene expression

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Created: Fri, 13 Aug 2010, 15:28:55 EST by Mr Yi Xin Ye on behalf of Library - Information Access Service