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<p>Nitrite reductase Nrf, encoded by the <i>nrf</i> operon, plays a central role in bacterial responses to nitrosative and oxidative stress under anaerobic conditions. In this study, we show that the pathogenic strain <i>Aeromonas veronii</i> C4 also expresses <i>nrf</i> and exhibits measurable nitrite reductase activity under aerobic growth conditions. Combined ChIP-seq and RNA-seq analyses identify ArgR as a direct negative regulator of <i>nrf</i> transcription. Biochemical assays further demonstrate that ArgR binds to the ARG box within the <i>nrf</i> promoter to repress its expression. Phylogenetic analyses reveal a correlated evolutionary pattern between ArgR and NrfA, and a conserved ARG box is present in the <i>nrf</i> promoters of most <i>Gammaproteobacteria</i>, suggesting that this regulatory mechanism is broadly conserved within this lineage. Functional assays show that deletion of <i>nrf</i> markedly reduces nitrite reduction and oxidative stress resistance under aerobic conditions. In addition, the expression of <i>nrf</i> and its associated electron-transfer genes (<i>pflB</i>, <i>fdoGHI</i>) varies with growth phase and environmental conditions and correlates with <i>argR</i> expression. ArgR transcription is not affected by nitrite but is responsive to arginine availability and oxidative stress, suggesting that ArgR primarily integrates metabolic and stress-related signals rather than nitrite itself. These observations are consistent with an ArgR–<i>nrf</i> regulatory link connecting nitrogen metabolism with aerobic redox stress adaptation, potentially contributing to bacterial fitness in host-associated environments.</p>

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ArgR regulates the nrf operon to defend against nitrosative and oxidative stress in Aeromonas veronii

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月31日

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  • Zucheng Wang,
  • Xiaoli Jiang,
  • Xiang Ma,
  • Yanqiong Tang,
  • Juanjuan Li,
  • Min Lin,
  • Zhu Liu

摘要

Nitrite reductase Nrf, encoded by the nrf operon, plays a central role in bacterial responses to nitrosative and oxidative stress under anaerobic conditions. In this study, we show that the pathogenic strain Aeromonas veronii C4 also expresses nrf and exhibits measurable nitrite reductase activity under aerobic growth conditions. Combined ChIP-seq and RNA-seq analyses identify ArgR as a direct negative regulator of nrf transcription. Biochemical assays further demonstrate that ArgR binds to the ARG box within the nrf promoter to repress its expression. Phylogenetic analyses reveal a correlated evolutionary pattern between ArgR and NrfA, and a conserved ARG box is present in the nrf promoters of most Gammaproteobacteria, suggesting that this regulatory mechanism is broadly conserved within this lineage. Functional assays show that deletion of nrf markedly reduces nitrite reduction and oxidative stress resistance under aerobic conditions. In addition, the expression of nrf and its associated electron-transfer genes (pflB, fdoGHI) varies with growth phase and environmental conditions and correlates with argR expression. ArgR transcription is not affected by nitrite but is responsive to arginine availability and oxidative stress, suggesting that ArgR primarily integrates metabolic and stress-related signals rather than nitrite itself. These observations are consistent with an ArgR–nrf regulatory link connecting nitrogen metabolism with aerobic redox stress adaptation, potentially contributing to bacterial fitness in host-associated environments.