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<p><i>Pseudomonas aeruginosa</i> is a Gram-negative opportunistic pathogen that causes severe acute and chronic infections, particularly in immunocompromised patients, those with cystic fibrosis, burn wounds, and structural lung disease. It has numerous virulence factors, including biofilm formation, quorum-sensing (QS) systems, exotoxins, and degradative enzymes, which make it pathogenic. All these factors combine to enhance tenaciousness, tissue destruction, and antimicrobial resistance. These virulence factors are being explored to inhibit multidrug-resistant microbes that are not susceptible to conventional antibiotics. Recent research has shown that synthetic molecules (such as enzyme antagonists, QS inhibitors, and novel chemical scaffolds), natural compounds (such as phytochemicals derived from plants, essential oils, and microbial metabolites), and synergistic combinations represent promising anti-virulence strategies. The use of nanomaterial-based synergistic delivery systems is vital for enhancing efficacy and targeted delivery. This review paper discusses the intriguing therapeutic properties of natural and synthetic agents, as well as their synergistic inhibitory effects, against various virulence factors that influence the strategies of multidrug-resistant bacteria, such as <i>P. aeruginosa</i>. Overall, these inhibitors enhance bactericidal activity by targeting multiple microbial pathways, with an emphasis on biofilm and QS systems, thereby addressing the problems of resilience and resistance development associated with conventional antibiotics. There are still issues with maximizing biocompatibility, pharmacokinetics, and clinical translation despite encouraging in vitro and preclinical results. This multifaceted strategy offers a lasting remedy for antibiotic-resistant <i>P. aeruginosa</i> infections, representing a paradigm shift from conventional bactericidal approaches to virulence attenuation. However, the possible adaptations of the pathogen and compensatory mutations to anti-virulence strategies need careful consideration.</p>

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Multiple virulence attenuating strategies against Pseudomonas aeruginosa: Natural, synthetic, and synergistic approaches

  • 期刊论文

  • 发表日期：

    2026年3月10日

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  • Mulugeta Mulat,
  • Nazia Tabassum,
  • Taehyeong Kim,
  • Fazlurrahman Khan

摘要

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen that causes severe acute and chronic infections, particularly in immunocompromised patients, those with cystic fibrosis, burn wounds, and structural lung disease. It has numerous virulence factors, including biofilm formation, quorum-sensing (QS) systems, exotoxins, and degradative enzymes, which make it pathogenic. All these factors combine to enhance tenaciousness, tissue destruction, and antimicrobial resistance. These virulence factors are being explored to inhibit multidrug-resistant microbes that are not susceptible to conventional antibiotics. Recent research has shown that synthetic molecules (such as enzyme antagonists, QS inhibitors, and novel chemical scaffolds), natural compounds (such as phytochemicals derived from plants, essential oils, and microbial metabolites), and synergistic combinations represent promising anti-virulence strategies. The use of nanomaterial-based synergistic delivery systems is vital for enhancing efficacy and targeted delivery. This review paper discusses the intriguing therapeutic properties of natural and synthetic agents, as well as their synergistic inhibitory effects, against various virulence factors that influence the strategies of multidrug-resistant bacteria, such as P. aeruginosa. Overall, these inhibitors enhance bactericidal activity by targeting multiple microbial pathways, with an emphasis on biofilm and QS systems, thereby addressing the problems of resilience and resistance development associated with conventional antibiotics. There are still issues with maximizing biocompatibility, pharmacokinetics, and clinical translation despite encouraging in vitro and preclinical results. This multifaceted strategy offers a lasting remedy for antibiotic-resistant P. aeruginosa infections, representing a paradigm shift from conventional bactericidal approaches to virulence attenuation. However, the possible adaptations of the pathogen and compensatory mutations to anti-virulence strategies need careful consideration.