Targeting antimicrobial drug resistance with marine natural products

Abstract

The rise and spread of antimicrobial resistance represents one of the most pressing health issues of today. Antimicrobial resistance in micro-organisms can arise due to a multiplicity of factors, including perme- ability changes in the cell membrane, increase of drug efflux pumps, enzymatic modification or inacti- vation of the antibiotic, target site modification, alternative metabolic pathways and biofilm formation. The marine environment is a valuable source of diverse natural products with a huge variety of biologi- cal activities. Among them, antimicrobial compounds show promising biological activities against numer- ous drug-resistant bacteria and fungi, making marine natural products a very promising resource in the search for novel antimicrobial agents. This review summarises the state-of-art of marine natural prod- ucts with antibacterial and antifungal properties against drug-resistant micro-organisms. These natural products were categorised based on their chemical structure, and their respective sources and activi- ties are highlighted. The chemical diversity associated with these marine-derived molecules is enormous, including peptides, polyketides, alkaloids, sterols, terpenoids, lactones, halogenated compounds, nucleo- sides, etc., some of which have rare substructures. Some of the marine compounds mentioned do not have intrinsic antimicrobial activity but potentiate the antimicrobial effect of other antimicrobials via in- hibition of efflux pumps. Although these agents are still in preclinical studies, evidence of their in vivo efficacy suggest research of new drugs from the ocean to overcome antimicrobial resistance in order to fulfil an unmet medical need.