Secondary Metabolites Governing Microbiome Interaction of Staphylococcal Pathogens and Commensals

Various Staphylococcus species colonize skin and upper airways of warm-blooded animals. They compete successfully with many other microorganisms under the hostile and nutrient-poor conditions of these habitats using mechanisms that we are only beginning to appreciate. Small-molecule mediators, whose biosynthesis requires complex enzymatic cascades, so-called secondary metabolites, have emerged as crucial components of staphylococcal microbiome interactions. Such mediators belong to a large variety of compound classes and several of them have attractive properties for future drug development. They include, for instance, bacteriocins such as lanthipeptides, thiopeptides, and fibupeptides that inhibit bacterial competitor species; signaling molecules such as thiolactone peptides that induce or inhibit sensory cascades in other bacteria; or metallophores such as staphyloferrins and staphylopine that scavenge scant transition metal ions. For some secondary metabolites such as the aureusimines, the exact function remains to be elucidated. How secondary metabolites shape the fitness of Staphylococcus species in the complex context of other microbial and host defense factors remains a challenging field of future research. A detailed understanding will help to harness staphylococcal secondary metabolites for excluding the pathogenic species Staphylococcus aureus from the nasal microbiomes of at-risk patients, and it will be instrumental for the development of advanced anti-infective interventions.