Comparative 'omics analyses differentiate Mycobacterium tuberculosis and Mycobacterium bovis and reveal distinct macrophage responses to infection with the human and bovine tubercle bacilli

• DOI: 10.1099/mgen.0.000163
• Publication Date: 2018-03-20T15:18:31Z
• Authors: Kerri M. Malone; Kévin Rue-Albrecht; David A. Magee; Kevin Conlon; Olga T. Schubert; Nicolas C. Nalpas; John A. Browne; Alicia Smyth; Eamonn Gormley; Ruedi Aebersold; David E. MacHugh; Stephen V. Gordon
• Keywords: Mycobacterium tuberculosis complex

Members of the Mycobacterium tuberculosis complex (MTBC) are causative agents in a range mammals, including humans. A key feature MTBC pathogens is their high degree genetic identity yet distinct host tropism. Notably, while bovis highly virulent and pathogenic for cattle, human pathogen M. attenuated cattle. Previous research also suggests that preference amongst members has basis innate immune responses. To explore tropism, we present in-depth profiling reference strains AF2122/97 H37Rv at both global transcriptional translational level via RNA-sequencing SWATH MS. Furthermore, bovine alveolar macrophage infection time course model was used to investigate shared divergent transcriptomic response with or AF2122/97. Significant differential expression virulence-associated pathways between two bacilli revealed, ESX-1 secretion system. observed macrophages, particular cytosolic DNA-sensing 48 h post-infection, highlights engagement The work presented here therefore provides identification mechanisms subverted by host-adapted mycobacteria promote survival during early stages infection.