Abstract
Tuberculosis, a lung disease caused by Mycobacterium tuberculosis (Mtb), is one of the ten leading causes of death worldwide affecting mainly developing countries. Mtb can persist and survive inside infected cells through modulation of host antibacterial attack, i.e., by avoiding the maturation of phagosome containing mycobacteria to more acidic endosomal compartment. In addition, bacterial phosphatases play a central role in the interplay between host cells and Mtb. In this study, we characterized the Rv2577 of Mtb as a potential alkaline phosphatase/phosphodiesterase enzyme. By an in vitro kinetic assay, we demonstrated that purified Rv2577 expressed in Mycobacterium smegmatis displays both enzyme activities, as evidenced by using the artificial substrates p-NPP and bis-(p-NPP). In addition, a three-dimensional model of Rv2577 allowed us to define the catalytic amino acid residues of the active site, which were confirmed by site-directed mutagenesis and enzyme activity analysis, being characteristic of a member of the metallophosphatase superfamily. Finally, a mutation introduced in Rv2577 reduced the replication of Mtb in mouse organs and impaired the arrest of phagosomes containing mycobacteria in early endosomes; which indicates Rv2577 plays a role in Mtb virulence.
Highlights
Tuberculosis (TB) is an infectious disease whose etiological agent is Mycobacterium tuberculosis (Mtb)
A BLASTp analysis demonstrated that Rv2577 shares about 25% of identity with purple acid phosphatase (PAP) of the metallophosphatase superfamily (MPP) (Supplementary Figure 1), a family mainly from plants, it is present in animals and fungi
Both domains are present in metallophosphoesterases, such as phosphoserine phosphatases, 5 -nucleotidases, sphingomyelin phosphodiesterases, 2,3 and 3,5 -cyclic-nucleotide phosphodiesterase as well as nucleases3
Summary
Tuberculosis (TB) is an infectious disease whose etiological agent is Mycobacterium tuberculosis (Mtb). The last report of the World Health Organization (WHO) informed that about a quarter of the world’s population is infected with Mtb, with the consequent risk of developing TB, and that an estimate of 10 million of new cases and 1.45 million deaths occurred in 20181. Rv2577: Virulence Factor, Phosphatase/Phosphodiesterase Enzyme even curable, disease, which affects mainly developing countries, is one of the ten leading causes of death worldwide. BCG only prevents young people from developing the disease and fails to protect the adult population. Even when the total number of TB cases has remained practically unchanged in recent years, there has been a marked geographic imbalance in the number of new cases because of co-infection with HIV, the emergence of multi and extreme resistant strains to the drugs historically used and the poor socio-economic conditions of the infected population
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
