Academics at the University College Dublin, University of Edinburgh, and ETH Zurich have made significant advances in understanding the disease bovine tuberculosis (bTB). This highly destructive disease affects cattle worldwide. The multi-faceted team has already identified a number of key genes and pathways involved. These findings contribute to how cattle react to infections caused by the bacteria Mycobacterium bovis, the pathogen that causes cattle TB. This game-changing research, appearing in the Science journal Communications Biology, paves the way for new tactics to control and combat this infectious disease. This disease continues to be a serious risk to animal and human health.
Bovine TB continues to be a long-standing problem in countries such as Ireland. It exerts a significant financial impact on national economies because of the need for intensive surveillance and control efforts. The researchers employed a transcriptome-wide association study (TWAS) to blend gene activity data with existing genome-wide association study (GWAS) data related to bTB susceptibility. This strategy allowed them to identify 115 genes associated with susceptibility to disease. These results have the power to revolutionize cattle diagnostics and breeding strategies.
Understanding M. bovis and Its Impact
Mycobacterium bovis is very similar to Mycobacterium tuberculosis, responsible for the vast majority of TB cases in humans. In truth, they are 99.95% genetically identical. This close relationship continues to expose us to the zoonotic threat that bTB poses. Second, it underscores the importance of eliminating the disease in cattle as a means to safeguard human populations. These discoveries shed new light on bovine immune responses. They may provide precious insights into human TB immunology.
Professor David MacHugh from the Animal Genomics Laboratory at UCD emphasized this connection:
"The close evolutionary relationship between the pathogens that cause TB in cattle and humans, coupled with similar host immune responses, means that these methods and results may be transferable to our species."
Genetic Variations and Disease Susceptibility
The research focused on identifying differences in gene activity in blood samples from bTB infected cattle. By combining this data with genome sequence information, researchers were able to pinpoint thousands of genomic changes that affect cellular function and behavior. Through their innovative computational analysis they identified 115 genes associated with bTB susceptibility. This groundbreaking work marks the first instance where genetic variations associated with bTB susceptibility have been directly connected to individual gene activity.
Professor Eamonn Gormley, Director of the bTB Diagnostics Laboratory at UCD, highlighted the significance of these findings:
"Our paper describes the first scientific study that directly links genetic variation underpinning bovine TB disease susceptibility to the activity of individual genes. Importantly, it signposts future research to develop new diagnostics and tools for breeding cattle with enhanced disease resilience."
John O'Grady, Ph.D. student and lead author of the study, further explained:
"Our results suggest that genetic variation affecting the initial proinflammatory immune response to M. bovis contributes to an animal contracting the disease as they are unable to effectively clear the infection."
Future Implications for Disease Management
This study offers important lessons that, if adopted, would go a long way toward strengthening bTB management. From these lessons learned, we can create more effective diagnostic tools and breeding strategies to increase disease resilience in our cattle. Together, these advancements will lead to a historic level of improvement in animal health. Simultaneously, they’ll mitigate the crushing economic burdens associated with efforts to control bovine TB.
Knowing the cellular and immunological pathways that are disrupted due to M. bovis infections can spark new studies. This can inform more innovative treatment and prevention strategies. John O'Grady noted:
"The study also provides important new information on the cellular and immunological pathways that are perturbed and reprogrammed by these infections."