Biology and applications of co-produced, synergistic antimicrobials from environmental bacteria

Environmental bacteria, such as Streptomyces spp., produce specialized metabolites that are potent antibiotics and therapeutics. Selected specialized antimicrobials are co-produced and function together synergistically. Co-produced antimicrobials comprise multiple chemical classes and are produced by a wide variety of bacteria in different environmental niches, suggesting that their combined functions are ecologically important. Here, we highlight the exquisite mechanisms that underlie the simultaneous production and functional synergy of 16 sets of co-produced antimicrobials. To date, antibiotic and antifungal discovery has focused mainly on single molecules, but we propose that methods to target co-produced antimicrobials could widen the scope and applications of discovery programs. This Review summarizes sixteen known co-produced bacterial metabolites, their biosynthesis strategies and their synergistic antimicrobial activity mechanisms.