The skin is the largest organ of the human body and acts as a shield against hazards such as harmful bacteria like Staphylococcus aureus . A diverse skin microbiota and immune cross talk control S. aureus numbers. S. aureus can bind to healthy skin and subsequently proliferate when the skin barrier is compromised, such as in a wound or in patients with atopic dermatitis (AD).

Staphylococci, whether beneficial commensals or pathogens, often colonize human skin, potentially leading to competition for the same niche. In this multidisciplinary study we investigate the structure, binding specificity, and mechanism of adhesion of the Aap lectin domain required forStaphylococcus epidermidisskin colonization and compare its characteristics to the lectin domain from the orthologousStaphylococcus aureusadhesin SasG. The Aap structure reveals a legume lectin-like fold with atypical architecture, showing specificity for N-acetyllactosamine and sialyllactosamine. Bacterial adhesion assays using human corneocytes confirmed the biological relevance of these Aap-glycan interactions. Single-cell force spectroscopy experiments measured individual binding events between Aap and corneocytes, revealing an extraordinarily tight adhesion force of nearly 900 nN and a high density of receptors at the corneocyte surface. The SasG lectin domain shares similar structural features, glycan specificity, and corneocyte adhesion behavior. We observe cross-inhibition of Aap- and SasG-mediated staphylococcal adhesion to corneocytes. Together, these data provide insights into staphylococcal interspecies competition for skin colonization and suggest potential avenues for inhibition ofS. aureuscolonization.

Antibiotic tolerance, which is a hallmark of persister bacteria, contributes to treatment-refractory infections and the emergence of heritable antimicrobial resistance. Drugs that reverse tolerance and persistence may become part of the arsenal to combat antimicrobial resistance.

The USA300 and USA600 clonal lineages are the cause of many serious Staphylococcus aureus infections. Here, we report the complete genomes of two methicillin-sensitive S. aureus strains isolated from the healthy skin of adults in Colorado, which are most phylogenetically similar to the USA300 and USA600 lineages.

Staphylococcus epidermidis is a ubiquitous skin commensal that has the potential to become pathogenic and cause disease. Here, we report the complete genome sequence of a S. epidermidis strain isolated from adult healthy skin that shows high expression of the virulence factor extracellular cysteine protease A (EcpA).