TY  - JOUR
A1  - Behera, Ananyaashree
A1  - Jain, Preeti
A1  - Ganguli, Geetanjali
A1  - Biswas, Mainak
A1  - Padhi, Avinash
A1  - Pattanaik, Kali Prasad
A1  - Nayak, Barsa
A1  - Ergün, Süleyman
A1  - Hagens, Kristine
A1  - Redinger, Natalja
A1  - Saqib, Mohd
A1  - Mishra, Bibhuti B.
A1  - Schaible, Ulrich E.
A1  - Karnati, Srikanth
A1  - Sonawane, Avinash
T1  - Mycobacterium tuberculosis acetyltransferase suppresses oxidative stress by inducing peroxisome formation in macrophages
JF  - International Journal of Molecular Sciences
N2  - Mycobacterium tuberculosis (Mtb) inhibits host oxidative stress responses facilitating its survival in macrophages; however, the underlying molecular mechanisms are poorly understood. Here, we identified a Mtb acetyltransferase (Rv3034c) as a novel counter actor of macrophage oxidative stress responses by inducing peroxisome formation. An inducible Rv3034c deletion mutant of Mtb failed to induce peroxisome biogenesis, expression of the peroxisomal β-oxidation pathway intermediates (ACOX1, ACAA1, MFP2) in macrophages, resulting in reduced intracellular survival compared to the parental strain. This reduced virulence phenotype was rescued by repletion of Rv3034c. Peroxisome induction depended on the interaction between Rv3034c and the macrophage mannose receptor (MR). Interaction between Rv3034c and MR induced expression of the peroxisomal biogenesis proteins PEX5p, PEX13p, PEX14p, PEX11β, PEX19p, the peroxisomal membrane lipid transporter ABCD3, and catalase. Expression of PEX14p and ABCD3 was also enhanced in lungs from Mtb aerosol-infected mice. This is the first report that peroxisome-mediated control of ROS balance is essential for innate immune responses to Mtb but can be counteracted by the mycobacterial acetyltransferase Rv3034c. Thus, peroxisomes represent interesting targets for host-directed therapeutics to tuberculosis.
KW  - peroxisome
KW  - Rv3034c
KW  - acetyltransferase
KW  - macrophages
KW  - oxidative stress
KW  - Mycobacterium tuberculosis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284080
SN  - 1422-0067
VL  - 23
IS  - 5
ER  -