Amino acids can deplete ATP and impair nitric oxide detoxification by Escherichia coli

Xuanqing Wan, Wen Kang Chou, Mark P. Brynildsen

Research output: Contribution to journalArticlepeer-review


Nitric oxide (·NO) is a prevalent antimicrobial that is known to damage iron-containing enzymes in amino acid (AA) biosynthesis pathways. With Escherichia coli, ·NO is detoxified in aerobic environments by Hmp, which is an enzyme that is synthesized de novo in response to ·NO. With this knowledgebase, it is expected that the availability of AAs in the extracellular environment would enhance ·NO detoxification, because AAs would foster translation of Hmp. However, we observed that ·NO detoxification by E. coli was far slower in populations grown and treated in the presence of AAs (AA+) in comparison to those grown and stressed in the absence of AAs (AA-). Further experiments revealed that AA+ populations had difficulty translating proteins under ·NO stress, and that ·NO activated the stringent response in AA+ populations. Additional work revealed significant ATP depletion in ·NO-stressed AA+ cultures that far exceeded that of ·NO-stressed AA- populations. Transcription, translation, and RelA were not found to be significant contributors to the ATP depletion observed, whereas AA import was implicated as a significant ATP consumption pathway. Alleviating ATP depletion while maintaining access to AAs partially restored ·NO detoxification, which suggested that ATP depletion contributed to the translational difficulties observed in ·NO-stressed AA+ populations. These data reveal an unexpected interaction within the ·NO response network of E. coli that stimulates a stringent response by RelA in conditions where AAs are plentiful.

Original languageEnglish (US)
Pages (from-to)90-99
Number of pages10
JournalFree Radical Biology and Medicine
StatePublished - Aug 20 2023

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Biochemistry


  • Flavohemoglobin
  • Hmp
  • NO
  • Stringent response
  • ppGpp


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