Deciphering the function of two component system PhoPR in Mycobacterium bovis

BLANCO, FEDERICO C; JACKSON, MARY; BARETTO, CECILIA; BIGI, FABIANA; GARCIA, ELIZABETH A.; PAZOS, ADRIANA

Santa Fé, Nueva México

Simposio; Tuberculosis: Immunity and immune evasion; 2020

Keystone Symposia on molecular and cellular biology

Mycobacterium bovis is the etiologic agent of bovine tuberculosis (TBB) and belongs to the Mycobacterium tuberculosis complex. M. bovis infects several mammalian animals of agricultural importance, wild animals and humans. Therefore, TBB is not only a problem for the economy but also a threat for public health. PhoP is a regulatory response protein that belongs to the two-component PhoPR system and is linked to the acid stress response in M. tuberculosis and M. bovis. The acid stress response requires balancing the redox state of the bacteria because the control of these pathways is crucial to regulate the metabolism and redistribution of cellular energy and thus survive in the host cell, the macrophage. The objective of this work is to elucidate the role of PhoP in the regulation of redox homeostasis and its metabolic adaptations for the survival of M. bovis against acid stress. We have previously found that the deletion of PhoP in an isolate of M. bovis reduces its virulence in murine model. RT-PCR analysis indicated that the lack of PhoP downregulates the expression of ureC (urease) and ansA (asparraginase) at low pH, suggesting that PhoP induces the production and secretion of ammonia to neutralize the external acidic environment. In addition, the di novo synthesis of phthiocerol dimycocerosates and triacylglycerol of phoP mutant was reduced compared to that of the wild type and the complementary strains, when the bacteria were under acidic stress. Altogether, these results suggest that in M. bovis PhoP plays a role of maintaing the redox homeostasis under stress conditions.