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<p>Imipenem, a critical antibiotic for treating multidrug-resistant <i>Pseudomonas aeruginosa</i>, now faces severe resistance from this pathogen. This study investigates the synergistic effects and underlying mechanisms of the combination of 2’’-O-galloylhyperin with imipenem against <i>P. aeruginosa.</i> 2’’-O-galloylhyperin showed no significant effect on the growth curve of strain 18102011 and its transconjugant D2011, while reducing the MIC of imipenem against this strain by 4-fold (FICI ≤ 0.5, synergy). This compound upregulates the citrate synthase gene <i>gltA</i>, and downregulates the aconitase gene <i>acnA</i>, enhancing citric acid synthesis while inhibiting its dehydration to cis-aconitase acid. Citric acid chelates Fe<sup>2+</sup>/Fe<sup>3+</sup>, reducing iron bioavailability, disrupting electron transfer, and increasing intracellular ROS levels in <i>P. aeruginosa</i> 18,102,011. Additionally, 2’’-O-galloylhyperin reduces the activity of the carbapenemase KPC-2. These findings highlight its potential as an adjuvant to enhance imipenem efficacy against <i>P. aeruginosa</i> infections.</p>

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2’’-O-galloylhyperin as a novel adjuvant to reduce imipenem resistance in multidrug-resistant Pseudomonas aeruginosa: transcriptome-based mechanism of iron homeostasis disruption

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月16日

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  • Lin Zheng,
  • Ge-Jin Lu,
  • Zi-xian Wang,
  • Xue-Jun Guo,
  • Zhen Wang,
  • Zhi-Ying Shao,
  • Ye-tao Wang,
  • Hua-Bin Jiang,
  • Shu-Tian Chen,
  • Feng-Yi Wang,
  • Jing Li,
  • Yuan-Qing Lin,
  • Si-Si Zheng,
  • Guang-Hui Lu,
  • Jun-Feng Qi,
  • Ling-Wei Zhu

摘要

Imipenem, a critical antibiotic for treating multidrug-resistant Pseudomonas aeruginosa, now faces severe resistance from this pathogen. This study investigates the synergistic effects and underlying mechanisms of the combination of 2’’-O-galloylhyperin with imipenem against P. aeruginosa. 2’’-O-galloylhyperin showed no significant effect on the growth curve of strain 18102011 and its transconjugant D2011, while reducing the MIC of imipenem against this strain by 4-fold (FICI ≤ 0.5, synergy). This compound upregulates the citrate synthase gene gltA, and downregulates the aconitase gene acnA, enhancing citric acid synthesis while inhibiting its dehydration to cis-aconitase acid. Citric acid chelates Fe2+/Fe3+, reducing iron bioavailability, disrupting electron transfer, and increasing intracellular ROS levels in P. aeruginosa 18,102,011. Additionally, 2’’-O-galloylhyperin reduces the activity of the carbapenemase KPC-2. These findings highlight its potential as an adjuvant to enhance imipenem efficacy against P. aeruginosa infections.