The vast majority of systemic bacterial infections are caused by facultative, often antibiotic-resistant, pathogens colonizing human body surfaces. Nasal carriage of Staphylococcus aureus predisposes to invasive infection, but the mechanisms that permit or interfere with pathogen colonization are largely unknown. Whereas soil microbes are known to compete by production of antibiotics, such processes have rarely been reported for human microbiota. We show that nasal Staphylococcus lugdunensis strains produce lugdunin, a novel thiazolidine-containing cyclic peptide antibiotic that prohibits colonization by S. aureus, and a rare example of a non-ribosomally synthesized bioactive compound from human-associated bacteria. Lugdunin is bactericidal against major pathogens, effective in animal models, and not prone to causing development of resistance in S. aureus. Notably, human nasal colonization by S. lugdunensis was associated with a significantly reduced S. aureus carriage rate, suggesting that lugdunin or lugdunin-producing commensal bacteria could be valuable for preventing staphylococcal infections. Moreover, human microbiota should be considered as a source for new antibiotics.

Staphylococcus aureus is usually regarded as a bacterial pathogen due to its ability to cause multiple types of invasive infections. Nevertheless, S. aureus colonizes about 30% of the human population asymptomatically in the nares, either transiently or persistently, and can therefore be regarded a human commensal as well, although carriage increases the risk of infection. Whereas many facets of the infection processes have been studied intensively, little is known about the commensal lifestyle of S. aureus . Recent studies highlight the major role of the composition of the highly variable nasal microbiota in promoting or inhibiting S. aureus colonization. Competition for limited nutrients, trace elements, and epithelial attachment sites, different susceptibilities to host defense molecules and the production of antimicrobial molecules by bacterial competitors may determine whether nasal bacteria outcompete each other. This chapter summarizes our knowledge about mechanisms that are used by S. aureus for efficient nasal colonization and strategies used by other nasal bacteria to interfere with its colonization. An improved understanding of naturally evolved mechanisms might enable us to develop new strategies for pathogen eradication.

In the interests of transparency, in this Article we wish to amend the competing financial interests statement to read: "Tuebingen University has filed a provisional patent application that covers the compound lugdunin and derivatives thereof, as well as the application of lugdunin-producing bacteria for the prevention of bacterial infections (European patent application number EP 15 160 285.1). " The online versions of the paper have been corrected.

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