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  - 
TY  - JOUR
A1  - Herweg, Jo-Ana
A1  - Hansmeier, Nicole
A1  - Otto, Andreas
A1  - Geffken, Anna C.
A1  - Subbarayal, Prema
A1  - Prusty, Bhupesh K.
A1  - Becher, Dörte
A1  - Hensel, Michael
A1  - Schaible, Ulrich E.
A1  - Rudel, Thomas
A1  - Hilbi, Hubert
T1  - Purification and proteomics of pathogen-modified vacuoles and membranes
JF  - Frontiers in Cellular and Infection Microbiology
N2  - Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation.
KW  - spectrometry-based proteomics
KW  - Mycobacterium tuberculosis
KW  - Chlamydia
KW  - Salmonella
KW  - bacterium Legionella pneumophila
KW  - endocytic multivesicular bodies
KW  - phagosome maturation arrest
KW  - III secretion system
KW  - endoplasmic reticulum
KW  - Chlamydia trachomatis
KW  - Simkania negevensis
KW  - intracellular bacteria
KW  - host pathogen interactions
KW  - immuno-magnetic purification
KW  - Legionella
KW  - Mycobacterium
KW  - Simkania
KW  - pathogen vacuole
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151823
VL  - 5
IS  - 48
ER  -