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<p>The global rise of multidrug-resistant pathogens, particularly methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), represents a critical public health challenge. This study evaluates the antibacterial and anti-biofilm activities of Derazantinib (ARQ-087) against <i>S. aureus</i>. ARQ-087 exhibited minimum inhibitory concentration (MIC) values ranging from 4 to 16 µM against <i>S. aureus</i> reference laboratory strains and diverse clinical MRSA isolates, demonstrating strong antibacterial activity with minimal resistance development. Time-kill assays demonstrated a concentration- and time-dependent reduction in bacterial viability. Crystal violet staining assays revealed that ARQ-087 significantly inhibited MRSA biofilm formation in a dose-dependent manner. Additionally, ARQ-087 exhibited strong anti-biofilm activity against pre-formed biofilms, as shown by colony counts and confocal laser scanning microscopy, which indicated extensive biofilm disruption and bacterial cell death. Mechanistic studies revealed that ARQ-087 disrupts bacterial membrane integrity, as evidenced by SYTOX Green and DISC3(5) fluorescence assays, while inducing intracellular ATP depletion and reactive oxygen species generation, contributing to bacterial death. ARQ-087 also displayed negligible hemolytic activity and no acute toxicity observed in a <i>Galleria mellonella</i> infection model. In this model, ARQ-087 prolonged the survival of larvae infected with <i>S. aureus</i>. These findings highlight ARQ-087 as a promising therapeutic candidate for treating MRSA infections and biofilm-associated diseases. Further preclinical studies are needed to confirm its potential for clinical application.</p>

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Antibacterial and anti-biofilm activities of Derazantinib (ARQ-087) against Staphylococcus aureus

  • 期刊论文

  • 发表日期：

    2025年3月6日

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  • Weiguo Wang,
  • Qiuxiang Zhong,
  • Xincheng Huang

摘要

The global rise of multidrug-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), represents a critical public health challenge. This study evaluates the antibacterial and anti-biofilm activities of Derazantinib (ARQ-087) against S. aureus. ARQ-087 exhibited minimum inhibitory concentration (MIC) values ranging from 4 to 16 µM against S. aureus reference laboratory strains and diverse clinical MRSA isolates, demonstrating strong antibacterial activity with minimal resistance development. Time-kill assays demonstrated a concentration- and time-dependent reduction in bacterial viability. Crystal violet staining assays revealed that ARQ-087 significantly inhibited MRSA biofilm formation in a dose-dependent manner. Additionally, ARQ-087 exhibited strong anti-biofilm activity against pre-formed biofilms, as shown by colony counts and confocal laser scanning microscopy, which indicated extensive biofilm disruption and bacterial cell death. Mechanistic studies revealed that ARQ-087 disrupts bacterial membrane integrity, as evidenced by SYTOX Green and DISC3(5) fluorescence assays, while inducing intracellular ATP depletion and reactive oxygen species generation, contributing to bacterial death. ARQ-087 also displayed negligible hemolytic activity and no acute toxicity observed in a Galleria mellonella infection model. In this model, ARQ-087 prolonged the survival of larvae infected with S. aureus. These findings highlight ARQ-087 as a promising therapeutic candidate for treating MRSA infections and biofilm-associated diseases. Further preclinical studies are needed to confirm its potential for clinical application.