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<p>Lymphatic filariasis (LF) remains a significant public health challenge, particularly in endemic regions where secondary bacterial infections exacerbate the morbidity associated with chronic lymphedema. Among these infections, <i>Pseudomonas aeruginosa</i> stands out due to its biofilm-forming ability and resistance to conventional antibiotics. This study underscores the importance of targeting <i>P. aeruginosa</i> in LF patients, as biofilm-associated infections are prevalent in chronic wounds, complicating treatment and increasing healthcare burdens. Leveraging molecular docking and molecular dynamics simulations, we screened 100 fungal polyketides against LasR and PqsR, quorum-sensing proteins critical to <i>P. aeruginosa</i> biofilm formation. Ketidocillinone B (Ket B) and Ketidocillinone C (Ket C) emerged as promising candidates with notable binding affinities of −9.3&#xa0;kcal/mol and −9.5&#xa0;kcal/mol to LasR, and −7.9&#xa0;kcal/mol and −8.8&#xa0;kcal/mol to PqsR, respectively. Molecular dynamics simulations revealed sustained stability of both compounds within the active sites, with binding energies of −82.559&#xa0;kJ/mol (Ket B) and −68.680&#xa0;kJ/mol (Ket C) for LasR, and −86.855&#xa0;kJ/mol (Ket B) and −90.342&#xa0;kJ/mol (Ket C) for PqsR. Pharmacokinetic evaluations indicated high gastrointestinal absorption, solubility, and favorable metabolic profiles, with Ket B exhibiting a clearance rate of 16.306&#xa0;mL/min/kg and Ket C 14.881&#xa0;mL/min/kg. These findings highlight the potential of Ket B and Ket C as therapeutic agents against <i>P. aeruginosa</i> infections in LF patients, through computational investigation. Future experimental validation could help by offering a novel approach to mitigate complications associated with this neglected tropical disease using KetB and Ket C as starting scaffold.</p>

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Computational insight into biofilm inhibitory activity of Ketidocillinone B and C against Pseudomonas aeruginosa: A way to combat Antibiotic Resistance among Filarial Lymphedema Patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月26日

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  • Prince Manu,
  • Prisca Baah Nketia,
  • Priscilla Osei-Poku,
  • Alexander Kwarteng

摘要

Lymphatic filariasis (LF) remains a significant public health challenge, particularly in endemic regions where secondary bacterial infections exacerbate the morbidity associated with chronic lymphedema. Among these infections, Pseudomonas aeruginosa stands out due to its biofilm-forming ability and resistance to conventional antibiotics. This study underscores the importance of targeting P. aeruginosa in LF patients, as biofilm-associated infections are prevalent in chronic wounds, complicating treatment and increasing healthcare burdens. Leveraging molecular docking and molecular dynamics simulations, we screened 100 fungal polyketides against LasR and PqsR, quorum-sensing proteins critical to P. aeruginosa biofilm formation. Ketidocillinone B (Ket B) and Ketidocillinone C (Ket C) emerged as promising candidates with notable binding affinities of −9.3 kcal/mol and −9.5 kcal/mol to LasR, and −7.9 kcal/mol and −8.8 kcal/mol to PqsR, respectively. Molecular dynamics simulations revealed sustained stability of both compounds within the active sites, with binding energies of −82.559 kJ/mol (Ket B) and −68.680 kJ/mol (Ket C) for LasR, and −86.855 kJ/mol (Ket B) and −90.342 kJ/mol (Ket C) for PqsR. Pharmacokinetic evaluations indicated high gastrointestinal absorption, solubility, and favorable metabolic profiles, with Ket B exhibiting a clearance rate of 16.306 mL/min/kg and Ket C 14.881 mL/min/kg. These findings highlight the potential of Ket B and Ket C as therapeutic agents against P. aeruginosa infections in LF patients, through computational investigation. Future experimental validation could help by offering a novel approach to mitigate complications associated with this neglected tropical disease using KetB and Ket C as starting scaffold.