| Summary: | Antibiotic monotherapy may become obsolete mainly due to the continuous emergence of resistance to available antimicrobials, which represents a major uncertainty to human health. Taking into account that natural products have been an inexhaustible source of new compounds with clinical application, lectins are certainly one of the most versatile groups of proteins used in biological processes, emerging as a promising alternative for therapy. The ability of lectins to recognize carbohydrates present on the cell surface allowed for the discovery of a wide range of activities. Currently the number of antimicrobials in research and development does not match the rate at which resistance mechanisms emerge to an effective antibiotic monotherapy. A promising therapeutic alternative is the combined therapy of antibiotics with lectins to enhance its spectrum of action, minimize adverse effects, and reduce resistance to treatments. Thus, this review provides an update on the experimental application of antibiotic therapies based on the synergic combination with lectins to treat infections specifically caused by multidrug-resistant and biofilm-producing <i>Staphylococcus aureus</i>, <i>Escherichia coli</i>, and <i>Pseudomonas aeruginosa</i>. We also briefly discuss current strategies involving the modulation of the gut microbiota, its implications for antimicrobial resistance, and highlight the potential of lectins to modulate the host immune response against oxidative stress.
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