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<p>The increasing prevalence of multidrug-resistant <i>Staphylococcus aureus</i> (MDRSA) and its ability to form biofilms on host tissues and indwelling devices necessitate the development of alternative therapeutic strategies beyond conventional bactericidal approaches. Two series of palladium(II) metal complexes, derived from α-picolinic acid and substituted anilines, namely QSL_Pd<sup>1A</sup> to QSL_Pd<sup>6A</sup> and QSL_Pd<sup>1B</sup> to QSL_Pd<sup>6B</sup>, were tested for their efficacy against multidrug-resistant (MDR) clinical isolates of <i>S.aureus</i>, SA P1966 and SA 2040, and their mechanism of action was elucidated. Among the complexes, QSL_Pd<sup>4A</sup> emerged as a potent lead, effectively suppressing biofilm formation with an MBIC₅₀ of 6.26–0.74&#xa0;µg/mL across both isolates in association with reduced extracellular polymeric substance production and lower cell surface hydrophobicity, without inducing reactive oxygen species. Gene expression analysis revealed downregulation of <i>sarA</i> and <i>icaA,</i> while the agr system remained unaffected. Notably, combinatorial therapy demonstrated a synergistic interaction with commercially available antibiotics, resensitizing the strains. Together, these findings highlight QSL_Pd<sup>4A</sup> as a promising antivirulence and antibiofilm agent that attenuates virulence factors, offering a viable strategy to combat MDRSA without exhibiting cytotoxicity.</p>

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Palladium(II) complexes suppress biofilm formation and virulence in multidrug-resistant Staphylococcus aureus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Rajaramon Shobana,
  • Selvam Sivaprakash,
  • Arlin Jose Amali,
  • Adline Princy Solomon,
  • Devarajan Suresh

摘要

The increasing prevalence of multidrug-resistant Staphylococcus aureus (MDRSA) and its ability to form biofilms on host tissues and indwelling devices necessitate the development of alternative therapeutic strategies beyond conventional bactericidal approaches. Two series of palladium(II) metal complexes, derived from α-picolinic acid and substituted anilines, namely QSL_Pd1A to QSL_Pd6A and QSL_Pd1B to QSL_Pd6B, were tested for their efficacy against multidrug-resistant (MDR) clinical isolates of S.aureus, SA P1966 and SA 2040, and their mechanism of action was elucidated. Among the complexes, QSL_Pd4A emerged as a potent lead, effectively suppressing biofilm formation with an MBIC₅₀ of 6.26–0.74 µg/mL across both isolates in association with reduced extracellular polymeric substance production and lower cell surface hydrophobicity, without inducing reactive oxygen species. Gene expression analysis revealed downregulation of sarA and icaA, while the agr system remained unaffected. Notably, combinatorial therapy demonstrated a synergistic interaction with commercially available antibiotics, resensitizing the strains. Together, these findings highlight QSL_Pd4A as a promising antivirulence and antibiofilm agent that attenuates virulence factors, offering a viable strategy to combat MDRSA without exhibiting cytotoxicity.