Controlling and treating biofilm-related infections is challenging because of the widespread presence of multidrug-resistant microbes. Biofilm, a naturally occurring matrix of microbial aggregates, has developed intricate and diverse resistance mechanisms against many currently used antibiotics. This poses a significant problem, especially for human health, including clinically chronic infectious diseases. Thus, there is an urgent need to search for and develop new and more effective antibiotics. As the marine environment is recognized as a promising reservoir of new biologically active molecules with potential pharmacological properties, marine natural products, particularly those of microbial origin, have emerged as a promising source of antibiofilm agents. Marine microbes represent an untapped source of secondary metabolites with antimicrobial activity. Furthermore, marine natural products, owing to their self-defense mechanisms and adaptation to harsh conditions, encompass a wide range of chemical compounds, including peptides and polyketides, which are primarily found in microbes. These molecules can be exploited to provide novel and unique structures for developing alternative antibiotics as effective antibiofilm agents. This review focuses on the possible antibiofilm mechanism of these marine microbial molecules against biofilm-forming pathogens. It provides an overview of biofilm development, its recalcitrant mode of action, strategies for the development of antibiofilm agents, and their assessments. The review also revisits some selected peptides and polyketides from marine microbes reported between 2016 and 2023, highlighting their moderate and considerable antibiofilm activities. Moreover, their antibiofilm mechanisms, such as adhesion modulation/inhibition targeting biofilm-forming pathogens, quorum sensing intervention and inhibition, and extracellular polymeric substance disruption, are highlighted herein.
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