AUTHOR=Sharma Tarina , Grover Sonam , Arora Naresh , P Manjunath , Ehtesham Nasreen Zafar , Hasnain Seyed Ehtesham 

TITLE=PGRS Domain of Rv0297 of Mycobacterium tuberculosis Is Involved in Modulation of Macrophage Functions to Favor Bacterial Persistence

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00451

DOI=10.3389/fcimb.2020.00451

ISSN=2235-2988

ABSTRACT=Mycobacterium tuberculosis (M.tb) Rv0297 encoded PE_PGRS5 has been known to be expressed at later stages of infection and in acidified phagosomes during transcriptome and proteomic studies.  The possible role of Rv0297 in modulation of phagosomal maturation and in providing protection against microbicidal environment has been hypothesized. We show that Rv0297PGRS is involved in modulating calcium homeostasis of macrophages followed by impedance of phagolysosomal acidification process. This is evident from the downregulation of late endosomal markers (Rab7 and Cathepsin D) in macrophages infected with recombinant Mycobacterium smegmatis - M.smeg_Rv0297 and M.smeg_Rv0297PGRS or treatment with recombinant Rv0297PGRS protein. Macrophages infected with rM.smeg expressing Rv0297 produce nitric oxide and undergo apoptosis, which may aid in dissemination of pathogen in later stages of infection. Rv0297 was also found to be involved in rescuing the bacterium from oxidative and hypoxic stress employed by macrophages and augmented survivability of the recombinant bacterium. These results attribute to the functional significance of this protein in M.tb virulence mechanism. The fact that this protein gets expressed at later stages of lung granulomas during M.tb infection suggests that the bacterium possibly employs Rv0297 as its dissemination and survival strategy.