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<p>Antimicrobial resistance (AMR) has become a global challenge in the treatment of infectious diseases. In 2024, the WHO updated the bacterial priority pathogens list, underscoring several high-priority resistant bacteria of major public health concern. Among these, Gram-negative bacteria are particularly prone to antibiotic resistance due to their complex outer membrane architecture. The reduced effectiveness of current therapies has resulted in an increasing global disease burden and mortality rates. <i>Pseudomonas aeruginosa</i> colonizes the upper respiratory tract and is frequently associated with secondary infections during viral pneumonia, contributing to increased complications. In the present study, we investigated the potentiality of plant-based Andrographolide and its derivatives. Initial screening identified four compounds along with the parent molecule (Andrographolide) that exhibited promising antipseudomonal activity, and among them, <b>IIIM(ND)-RS03</b> demonstrated greater inhibitory activity, which was further supported by Minimum Bactericidal Concentration (MBC) profiling, which shows a markedly lower bacterial colony count compared with the remaining molecules. Time-kill kinetics analysis revealed the bactericidal nature of the potent molecule, along with noteworthy biofilm inhibition and disruption potential with respect to the untreated control. Mechanistic studies revealed pronounced morphological alterations in bacterial cells, as confirmed by scanning electron microscopy analysis. Moreover, it can trigger multiple pathways that lead to cell death, including membrane disruption, increased permeability, reduction in intracellular ATP levels, and enhanced ROS generation. Taken together, the antibacterial activity as well as mechanistic insights, the present study underlines the potential of the selected molecule as a promising lead for the development of next-generation antimicrobial agents.</p> Graphical Abstract <p></p>

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Deciphering the potentiality of Andrographolide derivatives against Pseudomonas aeruginosa: in vitro analysis and mechanistic insights

  • 期刊论文

  • 发表日期：

    2026年3月18日

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  • Tashi Palmo,
  • Bhupesh K. Sharma,
  • Meenakshi Sharma,
  • Shazia Choudhary,
  • Ravi Shankar,
  • Kuljit Singh

摘要

Antimicrobial resistance (AMR) has become a global challenge in the treatment of infectious diseases. In 2024, the WHO updated the bacterial priority pathogens list, underscoring several high-priority resistant bacteria of major public health concern. Among these, Gram-negative bacteria are particularly prone to antibiotic resistance due to their complex outer membrane architecture. The reduced effectiveness of current therapies has resulted in an increasing global disease burden and mortality rates. Pseudomonas aeruginosa colonizes the upper respiratory tract and is frequently associated with secondary infections during viral pneumonia, contributing to increased complications. In the present study, we investigated the potentiality of plant-based Andrographolide and its derivatives. Initial screening identified four compounds along with the parent molecule (Andrographolide) that exhibited promising antipseudomonal activity, and among them, IIIM(ND)-RS03 demonstrated greater inhibitory activity, which was further supported by Minimum Bactericidal Concentration (MBC) profiling, which shows a markedly lower bacterial colony count compared with the remaining molecules. Time-kill kinetics analysis revealed the bactericidal nature of the potent molecule, along with noteworthy biofilm inhibition and disruption potential with respect to the untreated control. Mechanistic studies revealed pronounced morphological alterations in bacterial cells, as confirmed by scanning electron microscopy analysis. Moreover, it can trigger multiple pathways that lead to cell death, including membrane disruption, increased permeability, reduction in intracellular ATP levels, and enhanced ROS generation. Taken together, the antibacterial activity as well as mechanistic insights, the present study underlines the potential of the selected molecule as a promising lead for the development of next-generation antimicrobial agents.

Graphical Abstract