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.