Background: The golden era of antibiotic discovery from Actinomycetes peaked in the
middle of the 20th century and then got abandoned. Efforts to do a screening of synthetic compounds
libraries and rational target-based drug design were not successful and only a few new
classes of antibiotics have been described over the past 60 years.
Objective: This review summarizes the newest knowledge about two untapped sources of antibacterial
natural products - microorganisms and plants.
Methods: Research and review papers of the last decades were analyzed and the data were summarizes
to present the potential sources and mechanisms of natural products, which have the potential
to cope with staphylococcal infections.
Results: By using modern molecular biological methods, metagenomics and sequencing, it was
found out that Actinomycetes harbor many more operons coding for secondary metabolites with antimicrobial
potential than we can account for. Methods to grow uncultured microorganisms have
been developed and the uncultured microorganisms show promising potential for new antimicrobials.
The inhibition of pathogenicity of microorganisms via Quorum sensing inhibition, inhibition of
virulence factor production or biofilm formation by plant extracts offers new ways to control antibiotic-
resistant pathogens. Plant extracts with resistance modifying activity, e.g. efflux pumps inhibitors
used as antibiotic adjuvants have the potential to restore the therapeutic activity of drugs.
Conclusion: The findings from this review article confirm that new strategies, based on secondary
metabolites of Actinomycetes, uncultured microorganisms and plants may open new ways to overcome
the post-antibiotic era.