The Staphylococcus aureus-antagonizing human nasal commensal Staphylococcus lugdunensis depends on siderophore piracy

Background Bacterial pathogens such as Staphylococcus aureus colonize body surfaces of part of the human population, which represents a critical risk factor for skin disorders and invasive infections. However, such pathogens do not belong to the human core microbiomes. Beneficial commensal bacteria can often prevent the invasion and persistence of such pathogens by using molecular strategies that are only superficially understood. We recently reported that the commensal bacterium Staphylococcus lugdunensis produces the novel antibiotic lugdunin, which eradicates S. aureus from the nasal microbiomes of hospitalized patients. However, it has remained unclear if S. lugdunensis may affect S. aureus carriage in the general population and which external factors might promote S. lugdunensis carriage to enhance its S. aureus-eliminating capacity. Results We could cultivate S. lugdunensis from the noses of 6.3% of healthy human volunteers. In addition, S. lugdunensis DNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. Healthy S. lugdunensis carriers had a 5.2-fold lower propensity to be colonized by S. aureus indicating that lugdunin can eliminate S. aureus also in healthy humans. S. lugdunensis-positive microbiomes were dominated by either Staphylococcus epidermidis, Corynebacterium species, or Dolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated with S. lugdunensis, promoted S. lugdunensis growth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supportive commensals and on the capacity of S. lugdunensis to import siderophores. Conclusions These findings underscore the importance of microbiome homeostasis for eliminating pathogen colonization. Elucidating mechanisms that drive microbiome interactions will become crucial for microbiome-precision editing approaches.