Scholarlink

<p>Antimicrobial resistance (AMR) remains one of the most critical global health challenges, demanding innovative therapeutics beyond conventional antibiotics. In this study, <i>Pseudomonas aeruginosa</i> strain KAEH25, isolated from rhizospheric soil in Menoufia, Egypt, was identified as a potent producer of 1-hydroxyphenazine (1-HPZ), a redox-active phenazine derivative exhibiting broad-spectrum antimicrobial activity. The compound was extracted, purified, and characterized by ultraviolet–visible (UV–Vis) spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC), nuclear magnetic resonance spectroscopy (NMR), and gas chromatography–mass spectrometry (GC–MS), confirming its molecular identity and purity. To overcome its poor solubility and instability, 1-HPZ was encapsulated into mesoporous silica and magnetic Fe<sub>₃</sub>O<sub>₄</sub> nanoparticles. Nanomaterials were synthesized and characterized using dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM), confirming nanoscale uniformity, high surface area, and successful drug loading. Molecular docking studies (Schrödinger 2023-4) revealed strong binding affinities of 1-HPZ toward key bacterial enzymes including topoisomerase IV (–7.909&#xa0;kcal/mol), DNA gyrase (–6.650&#xa0;kcal/mol), and RNA polymerase (–6.750&#xa0;kcal/mol), implying multitarget inhibition of DNA replication, cell wall biosynthesis, and protein synthesis. Molecular dynamics simulations (Materials Studio 2024, COMPASS III) demonstrated favorable insertion energies (≈–4.8 × 10⁶ kcal/mol) for both free and nanoformulated 1-HPZ into <b>1</b>-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers, indicating strong membrane affinity and potential for enhanced cellular uptake. Experimentally, the 1-HPZ-loaded mesoporous nanoparticles showed the most potent antibacterial effect, producing inhibition zones up to 25&#xa0;mm against <i>Listeria monocytogenes</i> and <i>Escherichia coli</i>, surpassing free 1-HPZ. Time-kill and minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) assays confirmed bactericidal activity at low concentrations (MIC 4–16&#xa0;µg/mL; MBC 8–32&#xa0;µg/mL), outperforming both magnetic formulations and free 1-HPZ. These findings validate that mesoporous nanocarriers significantly enhance the solubility, stability, and antibacterial potency of 1-HPZ while maintaining biocompatibility. This integrated experimental and computational investigation demonstrates that coupling a microbial natural product with nanotechnology offers a promising route to overcome multidrug resistance. The 1-HPZ–mesoporous system provides a robust platform for next-generation antimicrobial therapies and magnetically guided drug delivery applications.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mesoporous and magnetic nanoparticle-based delivery of 1-hydroxyphenazine extracted from Pseudomonas aeruginosa enhances antimicrobial activity against different bacterial pathogens

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月20日

查看全文
  • Mahmoud Abd El-Mongy,
  • Khaled Abuelhaded,
  • Ahmed Hassan Ibrahim Faraag

摘要

Antimicrobial resistance (AMR) remains one of the most critical global health challenges, demanding innovative therapeutics beyond conventional antibiotics. In this study, Pseudomonas aeruginosa strain KAEH25, isolated from rhizospheric soil in Menoufia, Egypt, was identified as a potent producer of 1-hydroxyphenazine (1-HPZ), a redox-active phenazine derivative exhibiting broad-spectrum antimicrobial activity. The compound was extracted, purified, and characterized by ultraviolet–visible (UV–Vis) spectrophotometry, Fourier-transform infrared spectroscopy (FTIR), high-performance liquid chromatography (HPLC), nuclear magnetic resonance spectroscopy (NMR), and gas chromatography–mass spectrometry (GC–MS), confirming its molecular identity and purity. To overcome its poor solubility and instability, 1-HPZ was encapsulated into mesoporous silica and magnetic Fe₃O₄ nanoparticles. Nanomaterials were synthesized and characterized using dynamic light scattering (DLS), zeta potential, and transmission electron microscopy (TEM), confirming nanoscale uniformity, high surface area, and successful drug loading. Molecular docking studies (Schrödinger 2023-4) revealed strong binding affinities of 1-HPZ toward key bacterial enzymes including topoisomerase IV (–7.909 kcal/mol), DNA gyrase (–6.650 kcal/mol), and RNA polymerase (–6.750 kcal/mol), implying multitarget inhibition of DNA replication, cell wall biosynthesis, and protein synthesis. Molecular dynamics simulations (Materials Studio 2024, COMPASS III) demonstrated favorable insertion energies (≈–4.8 × 10⁶ kcal/mol) for both free and nanoformulated 1-HPZ into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers, indicating strong membrane affinity and potential for enhanced cellular uptake. Experimentally, the 1-HPZ-loaded mesoporous nanoparticles showed the most potent antibacterial effect, producing inhibition zones up to 25 mm against Listeria monocytogenes and Escherichia coli, surpassing free 1-HPZ. Time-kill and minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) assays confirmed bactericidal activity at low concentrations (MIC 4–16 µg/mL; MBC 8–32 µg/mL), outperforming both magnetic formulations and free 1-HPZ. These findings validate that mesoporous nanocarriers significantly enhance the solubility, stability, and antibacterial potency of 1-HPZ while maintaining biocompatibility. This integrated experimental and computational investigation demonstrates that coupling a microbial natural product with nanotechnology offers a promising route to overcome multidrug resistance. The 1-HPZ–mesoporous system provides a robust platform for next-generation antimicrobial therapies and magnetically guided drug delivery applications.