Genome-based Insights Into The Evolution And Function Of Enterococcus Faecium

The Genome-based research is an important approach to analyze thegenetic characteristics of bacteria, relationships among close relatedpathogenic strains and toxicity. This article is primarily based on genomicinformation to investigate Enterococcus faecium systematically.Enterococcus faecium is a commensal bacterium inhabiting in thegastrointestinal tract of human, and an important nosocomial pathogenwhich is often accompanied with a variety of antibiotics resistance. Somestudies suggested strains isolated from different environments often hadhighly divergent genomes. To illustrate this feature, firstly, thecomparative genome study of28E. faecium strains was performed. Then,we analyzed the phylogenetic relationships with methods of16S rRNA,the MLST and core genome respectively. After that, we studied a hospitalpathogen Enterococcus faecium C309by whole genome analysis andtried to establish a standard set of research strategy for the hospitalpathogens studies. In order to obtain a more complete genome, we haveadopted three different NGS platform (Roche454GS-FLX, Illumina GAIIx and ABI SOLiD4.0) to perform whole-genome sequencing. Then,we established a hybrid assembly method to integrate data from threeplatforms and constructed a more complete genome in comparison withusing any single platform data. In addition, the biases of platforms wereassessed, including biases of coverage depth, specific sequence biases(GC content and the k-mer diversity) and the bias from platform-specificsubstitution errors, to provide valuable guidelines for the genomeassembly. After acquiring C309genome sequence, the whole genomefunctional analysis was performed to character the major metabolicpathway, the source of specific proteins, antibiotic resistance andpotential toxicity. In all, our study helped form some guidelines to directgenomic work on other microorganisms, thus have important practicalimplications.The fourth chapter of the thesis described another major researchwork during the doctoral studies. In that section, we illustrated theexpression sensitivity of human disease-related genes. The genesassociated with distinct diseases reveals different expression perturbationsensitivities in various conditions. The diseases associated with robustgenes seem to be relatively lethal like cancer, aging andpharmacogenomic. On the other hand, the diseases associated withsensitive genes are apparently nonlethal like psych, chemdependency andreproduction diseases. Thus, this work may help to discover the etiologyand pathogenesis of common disease.