Amultifactorial assessment of the SRP pathway constituent FtsY as a vitalmycobacterial constituent

The signal recognition particle (SRP) system plays an imperative role in transporting the secretory protein to its intended location. The SRP pathway running in Mycobacterium tuberculosis constitutes FtsY (signal receptor), FfH (SRP), and 4.5S RNA in which signal receptor acts in the GTP-dependent manner. In this study, we are rendering the essential facts of FtsY with respect to mycobacterial growth. The growth study experiment showed that downexpressed FtsY slowed the growth of Mycobacterium smegmatis mc(2)155 from the initial lag phase to stationary phase. Previously, we have showed that GTPase activity of FtsY is metal ion dependent and showed the maximum activity with 10 mM magnesium. The effect of Mg2+ and Mn2+ on mycobacterial growth showed that Mg2+ did not affect the growth, whereas higher concentration of Mn2+ decreases the bacterial growth. After searching the inhibitor database, 14 GTPase and ATPase inhibitors, Mac0182344, ML141, ITX3, NAV_2729, Br-GTP, Rhosin_HCl, Mac0182099, CCG_50014, CID_1067700, Mac0174809, Nsc_23766, Berberine, Nexinhib20, and EHT1864, were found to interact with FtsY. Further, ML141 and NAV2729 found to decrease the enzymatic activity of FtsY as well as the mycobacterial growth. Therefore, the conclusive statement of the present study can be stated as that the FtsY playsmajor role inmycobacterial cell survival andML141 and NAV2729 can be used to constrain the SRP pathway.

Automated summary

The study highlights the important role of FtsY in mycobacterial growth, with inhibitors ML141 and NAV2729 identified as potential tools to constrain the SRP pathway.