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The Evolution Of Molecular Mimicry Of Bacterial Virulence Factor And BopA Gene Anti-Autophagy In B.Pseudomallei

Posted on:2016-08-15Degree:MasterType:Thesis
Country:ChinaCandidate:Z Q YinFull Text:PDF
GTID:2180330461990468Subject:Microbiology
Abstract/Summary:PDF Full Text Request
Bacteria, an ancient microorganism, have a close relationship with the development of human society. Pathogen is the case of many dangerous diseases, bring the threat to public life and health. During the process of pathogenesis, pathogens usual employ many kinds of virulence factor to interact with host and cause diseases. However, many virulence factors were found in non-pathogen, it is necessary to classify and analyze virulence systematically. We searched the orthologs of virulence factor in bacteria genomes using the reciprocal-best-BLAST-hits(RBH). According to whether be identified the orthologs in non-pathogen genomes, all virulence factors were divided into two types:pathogen specific-virulence factor and common virulence factor. As a result, most of virulence factor are common factor. We predict the molecular mimicry candidates in virulence factor by searching homologous sequences in human proteomes.The driving forces for the bacteria genome evolution are horizontal gene transfer, gene loss, gene mutation, gene recombination and so on. The study of the evolutionary dynamics can explore the origin or evolution of virulence mechanism of virulence factors. During the evolutionary dynamics between pathogens and hosts, pathogens have developed various strategies to survive in their hosts. Molecular mimicry is a common phenomenon by which pathogen microorganisms imitate host components to avoid immune responses and survive in host cells. Several pathogen microorganisms could produce factors that mimic the form or functions of host proteins to exploit cellular machinery and counter immune defenses. How molecular mimicry evolved is an intriguing problem. Up to now, host-to-pathogen horizontal gene transfer and convergent evolution have been proposed for the origination of pathogen molecular mimicry.In the present work, we chose the virulence factor neuB as the research object in the virulence factor database, which was annotated functionally as molecular mimicry. Virulence product of bacterial neuB gene is capsular polysaccharide, which is an important virulence factor of several pathogen. In order to clarify the evolutionary mechanism of neuB, we detect the distribution of neuB by searching homologous sequences. NeuB gene was widely distributed in bacteria and eukaryotes, including non-host non-pathogen and extreme environmental microorganisms. The significant sequence similarity was detected between bacterial and eukaryotic neuB. We construct the phylogenetic trees by sequence of neuB, the bacterial cluster forms a monophyletic group and segregated from the eukaryotic group. The nucleotide composition of neuB gene is basically consistent with host whole genome. Ultimately, our results support the possibility that the mimic neuB may arise via vertical transmission, which is a new evolutionary mechanism of molecular mimicry for bacterial.Autophagy is an important defense mechanism in eukaryotic cell targeting intracellular bacteria to restrict their survival and growth. On the other hand, several intracellular pathogens have developed the anti-autophagy mechanism to facilitate their own replication or intracellular survival. Up to now, no information about the origin or evolution of the anti-autophagic genes in bacteria is available. In the present study, the role of convergent evolution in evolving the ability of bacteria to evade autophagy is depicted. BopA is effector protein secreted by Burkholderia pseudomallei via the type three secretion systems, and it has been shown to play a pivotal role in their escape from autophagy. Sequence similarity searches for whole sequence and domain of BopA showed that homolog of BopA was not identified in eukaryotes. However, eukaryotic linear motifs-LIR motif was detected in BopA. Moreover, there was no obvious difference in GC content as well as CAI values of BopA gene and their respective genomes. These findings support the notion that the anti-autophagy function of BopA arose by convergent evolution.
Keywords/Search Tags:virulence factor, evolution, molecular mimicry, anti-autophagy
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