Comparative genomic and transcriptional analysis of virulent and non-virulent Haemophilus parasuis isolates

Authors: Nicholson, Tracy; Brunelle, Brian; Bayles, Darrell; Alt, David; Shore, Sarah

Submitted to: American Society for Microbiology General Meeting
Publication Type: Abstract Only
Publication Acceptance Date: 4/3/2017
Publication Date: N/A
Citation: N/A

Interpretive Summary:

Technical Abstract: Haemophilus parasuis is a respiratory pathogen of swine and the etiological agent of Glässer's disease, a systemic infection resulting in polyserositis, meningitis, and arthritis. H. parasuis isolates can exhibit different virulence capabilities ranging from lethal systemic disease to subclinical carriage. We hypothesized that genomic differences, including gene content and/or nucleotide variation, as well as gene expression differences among H. parasuis isolates are responsible for the range in the disease severity caused by H. parasuis strains. To identify genomic differences between phenotypically distinct strains, we obtained the closed whole-genome sequence and genome-wide methylation patterns for the highly virulent Nagasaki strain and for the non-virulent D74 strain. We identified 366 genes unique to Nagasaki and 324 genes unique to D74, including several putative Type I and Type III restriction modification systems, hemolysins, and other putative virulence-associated genes. Fourteen methylation motifs were identified in the Nagasaki genome and fifteen methylation motifs were identified in the D74 genome, with only one motif shared between the two genomes. To evaluate the contribution of gene expression differences, RNA sequencing was performed on Nagasaki and D74 after growth with and without 5% CO2. 284 genes were differentially expressed in strain D74 in response to 5% CO2, while only 36 genes were differentially expressed in strain Nagasaki. These data demonstrate that strain D74 is more transcriptionally responsive to carbon dioxide levels that mimic in vivo conditions within the respiratory tract and suggest that non-virulent H. parasuis strains may be more adaptive to colonization within the respiratory tract than virulent strains. Collectively, the unique genomic and transcriptional features identified in this study provide a foundation for understanding the genomic attributes responsible for the spectrum of virulent phenotypes that exist among H. parasuis isolates. This information is paramount to designing effective vaccines needed by the swine industry to mitigate H. parasuis disease burden.