Identification of Poly(ADP-ribose) Polymerase 9 (PARP9) as a Potent Suppressor for Mycobacterium tuberculosis Infection.

Abstract

ADP-ribosylation is a reversible and dynamic post-translational modification mediated by ADP-ribosyltransferases (ARTs). Poly(ADP-ribose) polymerases (PARPs) are an important family of human ARTs. ADP-ribosylation and PARPs have crucial functions in host-pathogen interaction, especially in viral infections. However, the functions and potential molecular mechanisms of ADP-ribosylation and PARPs in Mycobacterium infection remain unknown. In this study, bioinformatics analysis revealed significantly changed expression levels of several PARPs in tuberculosis patients compared to healthy individuals. Moreover, the expression levels of these PARPs returned to normal following tuberculosis treatment. Then, the changes in the expression levels of PARPs during Mycobacterium infection were validated in Tohoku Hospital Pediatrics-1 (THP1)-induced differentiated macrophages infected with Mycobacterium model strains bacillus Calmette-Guérin (BCG) and in human lung adenocarcinoma A549 cells infected with Mycobacterium smegmatis (Ms), respectively. The mRNA levels of PARP9, PARP10, PARP12, and PARP14 were most significantly increased during infection, with corresponding increases in protein levels, indicating the possible biological functions of these PARPs during Mycobacterium infection. In addition, the biological function of host PARP9 in Mycobacterium infection was further studied. PARP9 deficiency significantly increased the infection efficiency and intracellular proliferation ability of Ms, which was reversed by the reconstruction of PARP9. Collectively, this study updates the understanding of changes in PARP expression during Mycobacterium infection and provides evidence supporting PARP9 as a potent suppressor for Mycobacterium infection.

Supplementary information: The online version contains supplementary material available at 10.1007/s43657-023-00112-2.