Recipient Organization
UNIVERSITY OF MISSOURI
(N/A)
COLUMBIA,MO 65211
Performing Department
Veterinary Pathobiology
Non Technical Summary
Actinobacillus suis is a bacterial pathogen that causes septicemia in piglets and is an emerging problem for High Health Status swine. As a consequence, there is a significant negative impact on US agriculture. Little is known about how the organism causes disease, or why the bacterium can also be found in swine that are apparently healthy. Accordingly understanding how the bacterium is able to cause disease is important to developing strategies to prevent or treat infections. Determining the DNA sequence of most if not all of the genes of the bacterium Actinobacillus suis will provide the genetic blueprint of this important disease causing organism. New technologies for genome sequencing allow rapid and cost effective generation of this information. Analysis of the data generated will identify candidate targets for diagnostic applications, therapeutic intervention and an unprecedented perspective on how the bacterium causes disease.
Animal Health Component
10%
Research Effort Categories
Basic
80%
Applied
10%
Developmental
10%
Goals / Objectives
Actinobacillus suis is a porcine pathogen that is a causative agent of fatal septicemia in piglets and an emerging pathogen of older High Health Status swine. Despite its increasing importance, very little is known about the pathogenesis of A. suis. This is further complicated by the reported isolation of the organism from healthy animals. With the advent of novel DNA sequencing technologies it is now possible to generate high quality draft genome sequences of many bacterial species at substantially reduced costs. Through draft genome sequencing and analysis, the results of this project are expected to have tremendous benefit to translational research applications, particularly in the areas of pathogenesis, surveillance, epidemiology, treatment and prevention, which can now be viewed from the level of the genome. The project will also generate fundamental new insights into the biology and evolution of this important emerging animal pathogen. Comparative analysis with related species will offer a unique perspective of the differential virulence of closely related bacterial species. The sequences generated will be publically accessible and will be a critical adjunct to research by other members of the scientific community.
Project Methods
To generate a draft genome sequence of A. suis within the budget of this application, massively parallel pyrosequencing using the '454' technology will be performed. As originally released, this method is able to generate approx. 20 million bases (Mb) of DNA sequence in a single overnight run. Recent advances have increased this capability to greater than 34 Mb of sequence, representing a 20-fold coverage for the estimated 2.3-Mb genome of A. suis. Because of the relatively short sequence reads (250 bp), the data will likely not produce a complete genome, but rather will provide greater than 99 percent of the genome sequence, in multiple sections. The sequence data will be analyzed to identify open reading frames (ORFs) and non-ORF genome features, annotate ORFs and intra- and intergenomic analyses. Effort will be given to identify putative virulence factors and potential diagnostic targets. Comparison of this genome to closely related pathogens should provide new insights and context concerning their ecology and evolution. The broader impacts of this study will occur on several research fronts. The data will provide a platform from which hypothesis driven federal grant applications can be envisaged and submitted that address aspects of pathogenesis. Candidate diagnostic targets will be identified and strategies for improved control and treatment can be developed. The generation of a genomic perspective through which to study this organism will be of tremendous benefit to the scientific community already studying this pathogen. Availability of genomic resources for A. suis will surely precipitate an expansion in the nature of investigations conducted and the number of researchers interested in its study.