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Published on: May 5, 2016
Palladium(II) complexes suppress biofilm formation and virulence in multidrug-resistant Staphylococcus aureus
Rajaramon Shobana1, Selvam Sivaprakash2, Arlin Jose Amali2
1Quorum Sensing LaboratoryCentre for Research in Infectious Diseases (CRID)School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, 613401, India.
Abstract:
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.
Insights
New palladium(II) complexes show promise against multidrug-resistant Staphylococcus aureus (MDRSA). The compound QSL_Pd4A effectively inhibits biofilm formation and virulence, offering a potential alternative to traditional antibiotics.
Area of Science:
- Medicinal Chemistry
- Microbiology
- Materials Science
Background:
- Rising prevalence of multidrug-resistant Staphylococcus aureus (MDRSA) necessitates novel therapeutic strategies.
- MDRSA's biofilm formation poses challenges for conventional bactericidal treatments.
Purpose of the Study:
- To synthesize and evaluate palladium(II) metal complexes for activity against MDRSA.
- To elucidate the mechanism of action of promising compounds, focusing on biofilm inhibition and virulence attenuation.
Main Methods:
- Synthesis of two series of palladium(II) complexes (QSL_Pd1A-6A and QSL_Pd1B-6B).
- Testing efficacy against MDR clinical isolates of S. aureus (SA P1966 and SA 2040).
- Assessing biofilm formation, extracellular polymeric substance production, cell surface hydrophobicity, and gene expression (sarA, icaA, agr).
Main Results:
- QSL_Pd4A demonstrated potent antibiofilm activity (MBIC50: 6.26-0.74 µg/mL) against both isolates.
- QSL_Pd4A reduced biofilm formation by decreasing extracellular polymeric substance and cell surface hydrophobicity, without inducing reactive oxygen species.
- Gene expression analysis showed downregulation of sarA and icaA, while the agr system was unaffected.
- Combinatorial therapy with QSL_Pd4A and existing antibiotics showed synergistic effects, resensitizing MDRSA strains.
Conclusions:
- QSL_Pd4A is a promising antivirulence and antibiofilm agent against MDRSA.
- This compound offers a viable strategy to combat MDRSA by attenuating virulence factors.
- The palladium(II) complex shows potential for developing new therapies against resistant bacterial infections without cytotoxicity.
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