No abstract

Control of mycobacterial infection constitutes a priority for human and animal health worldwide. However, effective vaccines are needed for the control of human and animal tuberculosis (TB). Adult zebrafish have become a useful model for studying the pathophysiology of mycobacterial infection and for the development of novel interventions for TB control and prevention. Recently, parenteral and oral immunization with the heat-inactivated Mycobacterium bovis vaccine (M. bovis IV) protected wild boar against TB. The objectives of this study were to provide additional support for the role of M. bovis IV in TB control using the zebrafish model and to conduct the first trial with this vaccine for the control of fish mycobacteriosis. The results showed that M. bovis IV protected zebrafish against mycobacteriosis caused by low and high infection doses of Mycobacterium marinum and provided evidence suggesting that the protective mechanism elicited by M. bovis IV in zebrafish as in other species is based on the activation of the innate immune response through the C3 pathway, with a role for the regulatory protein Akr2 in this process. These results encourage the use of M. bovis IV for TB control in different species.

One of the major challenges in modern biology is the use of large omics datasets for the characterization of complex processes such as cell response to infection. These challenges are even bigger when analyses need to be performed for comparison of different species including model and non-model organisms. To address these challenges, the graph theory was applied to characterize the tick vector and human cell protein response to infection with Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis. A network of interacting proteins and cell processes clustered in biological pathways, and ranked with indexes representing the topology of the proteome was prepared. The results demonstrated that networks of functionally interacting proteins represented in both infected and uninfected cells can describe the complete set of host cell processes and metabolic pathways, providing a deeper view of the comparative host cell response to pathogen infection. The results demonstrated that changes in the tick proteome were driven by modifications in protein representation in response to A. phagocytophilum infection. Pathogen infection had a higher impact on tick than human proteome. Since most proteins were linked to several cell processes, the changes in protein representation affected simultaneously different biological pathways. The method allowed discerning cell processes that were affected by pathogen infection from those that remained unaffected. The results supported that human neutrophils but not tick cells limit pathogen infection through differential representation of ras-related proteins. This methodological approach could be applied to other host-pathogen models to identify host derived key proteins in response to infection that may be used to develop novel control strategies for arthropod-borne pathogens.