Different transcriptional regulatory activities of Mycobacterium bovis and Mycobacterium tuberculosis PhoPR systems

Tuberculosis (TB) is an infectious disease that affects humans and animals. The pathogens that cause TB belong to the Mycobacterium tuberculosis complex (MTBC), with M. tuberculosis and Mycobacterium bovis as the main representatives of human- and animal-adapted strains, respectively. One key genetic regulator of the MTBC members is the PhoPR system, which controls many processes, including the stress response, lipid metabolism and pathogenesis, among others. Previous studies identified a key G71I substitution in the M. bovis PhoR orthologue relative to M. tuberculosis PhoR and suggested that PhoPR might be non-functional in animal-adapted strains, but recent work has highlighted the functionality of PhoPR in M. bovis despite the G71I substitution. Here, we compare the transcriptional effects of the PhoPR system of M. tuberculosis H37Rv and M. bovis AF2122/97 on an M. bovis AF2122/97 ΔphoPR knockout background. Our results show common patterns of gene expression between the two orthologues, but also clear differences in the expression of rubredoxin genes and lipid biosynthetic loci. This work adds to the evidence that the PhoPR system is indeed functional in M. bovis and suggests that PhoPR controls differential transcriptional programmes that are important in the adaptation to human or animal hosts.