Submitted to: Microbial Pathogenesis
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/22/2009
Publication Date: 4/1/2009
Citation: Wu, C., Schmoller, S.K., Bannantine, J.P., Eckstein, T.M., Inamine, J.M., Livesey, M., Albrecht, R., Talaat, A. 2009. A Novel Cell Wall Lipopeptide Is Important for Biofilm Formation and Pathogenicity of Mycobacterium avium subspecies paratuberculosis. Microbial Pathogenesis. 46(4):222-230. Interpretive Summary: This manuscript describes the thorough characterization of an artificially induced genetic mutation in the bacterium that causes Johne’s disease. The mutation was located in a very large gene called pstA. Because of this mutation, the bacterium, called Mycobacterium avium subspecies paratuberculosis, was not able to produce biofilms. Biofilms consist of a mass of biological material that sticks tightly to materials and is difficult to disrupt. Additional experiments also suggest that this gene may play a role in invasion of epithelial cells. Epithelial cell invasion is an initial step in causing the infection that ultimately gives rise to Johne’s disease. Findings from this study have important implications for the pathogenesis of Johne’s disease.
Technical Abstract: Biofilm formation by pathogenic bacteria plays a key role in their pathogenesis. Previously, the pstA gene was shown to be involved in the virulence of Mycobacterium avium subspecies paratuberculosis (M. ap), the causative agent of Johne's disease in cattle and a potential risk factor for Crohn's disease. Scanning electron microscopy and colonization levels of the M. ap mutant indicated that the pstA gene significantly contributes to the ability of M. ap to form biofilms. Digital measurements taken during electron microscopy identified a unique morphology for the Delta pstA mutant, which consisted of significantly shorter bacilli than the wild type. Analysis of the lipid profiles of the mycobacterial strains identified a novel lipopeptide that was present in the cell wall extracts of wild-type M. ap, but missing from the Delta pstA mutant. Interestingly, the calf infection model suggested that pstA contribute to intestinal invasion of M. ap. Furthermore, immunoblot analysis of peptides encoded by pstA identified a specific and significant level of immunogenicity. Taken together, our analysis revealed a novel cell wall component that could contribute to biofilm formation and to the virulence and immunogenicity of M. ap. Molecular tools to better control M. ap infections could be developed utilizing the presented findings.