Perspectives on the enhancement of commercially available antibiotics by natural products

Abstract

Background: Opportunistic resistant bacteria are health and economically relevant in the health care systems and in industries worldwide, especially in the so-called resistant bacteria era (RBE). Enhancing the activity of commercially available antibiotics (CAAs) with di erent types of natural products (NPs) is a successful antimicrobial strategy, for instance the amoxicillin and clavulanate mixture. Objective: To nd research trends in this eld during 2015-2020 and to detect potential drug hits with potential to diversify formulations and materials design that can be useful to manage the RBE. Systematic review results: It yielded 190 reports of synergistic e ects of CAAs and NPs. The analyzed variables were: a) natural products origin: plant family, genera, secondary metabolite type; b) strains: +/- Gram, genera, most frequent species, application eld; and c) CAAs: family, most frequent CAAs. The families with potential to have more bioactive species were Apocynaceae, Rubiaceae, Euphorbiaceae (Isbio factor). Lonicera had the highest reports amount. Polyphenols and avonoids were the majority of pure NPs tested. Several potential drug hits for antibiotic activity enhancement at synergistic level were identi ed together with potential mechanisms of action: berberine (drug e ux inhibitor{DEI, bio lm inhibitor{BI), curcumin (BI), essential oils (BI), 3-o-metyl-butylgallato (inhibition of fatty acid saturation), among others. About the half of the tested strains were gram positive, being Methicillin Resistant Staphylococcus aureus (MRSA) the most frequently tested. Escherichia coli was the gram negative strain most frequently reported, including enterotoxigenic and extended spectrum beta-lactamases producers. The growth of other foodborne genera strains, such as Listeria and Salmonella, were also inhibited. Aminoglycosides were the family most reported, with gentamicin as the most commonly studied. Conclusions: NPs as either as plant extracts from a variety of families, or as puri ed compounds specially avonoids and polyphenols, have shown e ective results to enhance the antibiotic activity of CAAs against gram positive and negative strains relevant to HC and FI. Their mechanisms of action are starting to be determined, as the case EPIs and BIs. Further research is needed to achieve co-formulations and materials design useful for those elds, that can certainly be positively impacted by pursuing this strategy.