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- W4386950227 abstract "Abstract Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mtb ( Mycobacterium tuberculosis ), but the underlying mechanism remains unknown. Here, we report that L-alanine interacted with PRSS1 and unfroze the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzed L-alanine and reduced the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associated with TAK1 and disrupted the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disabled PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene β-defensin 4 ( Defb4 ) impaired the virulence by Rv2780 during infection in mice. Both L-alanine or the Rv2780 inhibitor, GWP-042, exhibited excellent inhibitory activity against M. tuberculosis infection in vivo . Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis ." @default.
- W4386950227 created "2023-09-23" @default.
- W4386950227 creator A5004461219 @default.
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- W4386950227 date "2023-09-22" @default.
- W4386950227 modified "2023-10-15" @default.
- W4386950227 title "Pathogenic mycobacteria suppress host antimicrobial peptides by dehydrogenating L-alanine" @default.
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