Abstract
The universal stress protein family is a family of stress-induced proteins. Universal stress proteins affect latency and antibiotic resistance in mycobacteria. Here, we showed that Mycobacterium smegmatis overexpressing M. tuberculosis universal stress protein Rv2624c exhibits increased survival in human monocyte THP-1 cells. Transcriptome analysis suggested that Rv2624c affects histidine metabolism, and arginine and proline metabolism. LC-MS/MS analysis showed that Rv2624c affects the abundance of arginine, a modulator of both mycobacteria and infected THP-1 cells. Biochemical analysis showed that Rv2624c is a nucleotide-binding universal stress protein, and an Rv2624c mutant incapable of binding ATP abrogated the growth advantage in THP-1 cells. Rv2624c may therefore modulate metabolic pathways in an ATP-dependent manner, changing the abundance of arginine and thus increasing survival in THP-1 cells.
Highlights
The universal stress protein family is a family of stress-induced proteins
Rv2623 is the first mycobacterial universal stress protein identified that has been shown to be involved in M. tuberculosis persistence in vivo and to regulate mycobacterial growth in vitro[13]
We have shown that Rv2624c overexpression in mycobacteria increases their survival in the Wayne mycobacterial latency model and in human monocyte THP-1 cells
Summary
The universal stress protein family is a family of stress-induced proteins. Universal stress proteins affect latency and antibiotic resistance in mycobacteria. We showed that Mycobacterium smegmatis overexpressing M. tuberculosis universal stress protein Rv2624c exhibits increased survival in human monocyte THP-1 cells. LC-MS/MS analysis showed that Rv2624c affects the abundance of arginine, a modulator of both mycobacteria and infected THP-1 cells. Biochemical analysis showed that Rv2624c is a nucleotide-binding universal stress protein, and an Rv2624c mutant incapable of binding ATP abrogated the growth advantage in THP-1 cells. Rv2624c has been shown to be an immunogenic protein, the antibody against Rv2624c being detected in serum from TB patients serum[16] These studies suggest that Rv2624c affects the infected host cell immune response. We showed that Rv2624c increases the survival of mycobacteria in hypoxia and bacillary-infected THP-1 cells. The growth advantage in THP-1 cells is ATP dependent, as an Rv2624c mutant incapable of ATP-binding abrogated the growth advantage of M. smegmatis mc2155 cells overexpressing Rv2624c
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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 call