Abstract:
:The human pathogen Mycobacterium tuberculosis encodes a proteasome that carries out regulated degradation of bacterial proteins. It has been proposed that the proteasome contributes to nitrogen metabolism in M. tuberculosis, although this hypothesis had not been tested. Upon assessing M. tuberculosis growth in several nitrogen sources, we found that a mutant strain lacking the Mycobacterium proteasomal activator Mpa was unable to use nitrate as a sole nitrogen source due to a specific failure in the pathway of nitrate reduction to ammonium. We found that the robust activity of the nitrite reductase complex NirBD depended on expression of the groEL/groES chaperonin genes, which are regulated by the repressor HrcA. We identified HrcA as a likely proteasome substrate, and propose that the degradation of HrcA is required for the full expression of chaperonin genes. Furthermore, our data suggest that degradation of HrcA, along with numerous other proteasome substrates, is enhanced during growth in nitrate to facilitate the derepression of the chaperonin genes. Importantly, growth in nitrate is an example of a specific condition that reduces the steady-state levels of numerous proteasome substrates in M. tuberculosis.
journal_name
Proc Natl Acad Sci U S Aauthors
Becker SH,Jastrab JB,Dhabaria A,Chaton CT,Rush JS,Korotkov KV,Ueberheide B,Darwin KHdoi
10.1073/pnas.1819468116subject
Has Abstractpub_date
2019-02-19 00:00:00pages
3202-3210issue
8eissn
0027-8424issn
1091-6490pii
1819468116journal_volume
116pub_type
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