Siderophore piracy enables the nasal commensalStaphylococcus lugdunensisto antagonize the pathogenStaphylococcus aureus

Abstract

AbstractBacterial pathogens such asStaphylococcus aureuscolonize 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 persistence of certain pathogens – using molecular strategies that are only superficially understood. We recently reported that the commensal bacteriumStaphylococcus lugdunensisproduces the novel antibiotic lugdunin, which eradicatesS. aureusfrom nasal microbiomes of hospitalized patients. However, it has remained unclear ifS. lugdunensismay affectS. aureuscarriage in the general population and howS. lugdunensiscarriage could be promoted to enhance itsS. aureus-eliminating capacity. We could cultivateS. lugdunensisfrom the noses of 6.3% of healthy human volunteers. In addition,S. lugdunensisDNA could be identified in metagenomes of many culture-negative nasal samples indicating that cultivation success depends on a specific bacterial threshold density. HealthyS. lugdunensiscarriers had a 5.2-fold lower propensity to be colonized byS. aureusindicating that lugdunin can eliminateS. aureusalso in healthy humans.S. lugdunensis-positive microbiomes were dominated by eitherStaphylococcus epidermidis,Corynebacteriumspecies, orDolosigranulum pigrum. These and further bacterial commensals, whose abundance was positively associated withS. lugdunensis, promotedS. lugdunensisgrowth in co-culture. Such mutualistic interactions depended on the production of iron-scavenging siderophores by supporting commensals, and on the capacity ofS. lugdunensisto import siderophores. 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.