AI Article Synopsis

  • Human macrophages produce reactive nitrogen species in response to Mycobacterium tuberculosis infection, which causes stress in the bacteria and affects protein modifications.
  • Researchers analyzed the acylation of Mtb proteins after exposure to low levels of nitric oxide, identifying 6,437 acylation events in 1,496 proteins, predominantly O-acylation.
  • The study highlights how protein acylation may influence Mtb's responses to stress and antimicrobial resistance, marking the first comprehensive profiling of Mtb's acylation due to nitrosative stress, which could inform global health strategies.

Article Abstract

Background: Human macrophages generate antimicrobial reactive nitrogen species in response to infection by Mycobacterium tuberculosis (Mtb). Exposure to these redox-reactive compounds induces stress response in Mtb, which can affect posttranslational modifications (PTM).

Methods: Here, we present the global analysis of the PTM acylation of Mtb proteins in response to a sublethal dose of nitrosative stress in the form of nitric oxide (NO) using label free quantification.

Results: A total of 6437 acylation events were identified on 1496 Mtb proteins, and O-acylation accounted for 92.2% of the events identified, while 7.8% were N-acylation events. About 22% of the sites identified were found to be acylated by more than one acyl-group. Furthermore, the abundance of each acyl-group decreased as their molecular weight increased. Quantitative PTM analysis revealed differential abundance of acylation in proteins involved in stress response, iron ion homeostasis, growth, energy metabolism, and antimicrobial resistance (AMR) induced by nitrosative stress over time.

Conclusions: The results reveal a potential role of Mtb protein acylation in the bacterial stress responses and AMR. To our knowledge, this is the first report on global O-acylation profile of Mtb in response to NO. This will significantly improve our understanding of the changes in Mtb acylation under nitrosative stress, highly relevant for global health.

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Source
http://dx.doi.org/10.1002/prca.202300212DOI Listing

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