Marine natural products as potential anti-Pseudomonas aeruginosa agents: challenges and advances.

Antimicrobial resistance (AMR) has become a pressing need to address in the major global public health challenges, posing a serious threat to human health. Pseudomonas aeruginosa (PA) is one of the most concerning Gram-negative pathogens and is typically treated with broad-spectrum antibiotics. PA exhibits resistance to multiple antibiotics, multifactorial virulence, and dynamic hyperadaptation, which results in a particularly formidable challenge in eliminating PA from patients. The problem of drug resistance is becoming increasingly serious, and the development of new antibiotics is extremely lagging behind, resulting in no drug with a new structure and mechanism being approved for the treatment of infections caused by drug-resistant Gram-negative bacteria over the past half-century. Consequently, the development of new antibiotics is of utmost urgency and importance. Marine natural products (MNPs) have become an important source for developing new antibiotics due to their unique properties. So far, 44 potential molecules with significant anti-PA activity have been isolated from marine organisms, of which 19 have been reported as quorum-sensing system inhibitors (QSIs) with potential for further development. In this review, we provide a comprehensive summary of the current status of drug resistance, pathogenic mechanisms, and resistance mechanisms associated with PA infections. We also highlight the challenges and opportunities presented by MNPs in the development of anti-PA drugs, and offer recommendations to accelerate the antibiotic development process, thereby providing valuable insights for the study and exploitation of novel antibiotics.