BackgroundStaphylococcus aureus (SA) nasal colonization plays a critical role in the pathogenesis of staphylococcal infections and SA eradication from the nares has proven to be effective in reducing endogenous infections. To understand SA nasal colonization and its relation with consequent disease, assessment of nasal carriage dynamics and genotypic diversity among a diverse population is a necessity.ResultsWe have performed extensive longitudinal monitoring of SA nasal carriage isolates in 109 healthy individuals over a period of up to three years. Longitudinal sampling revealed that 24% of the individuals were persistent SA nasal carriers while 32% were intermittent. To assess the genetic relatedness between different SA isolates within our cohort, multi locus sequence typing (MLST) was performed. MLST revealed that not only were strains colonizing intermittent and persistent nasal carriers genetically similar, belonging to the same clonal complexes, but strain changes within the same host were also observed over time for both types of carriers. More highly discriminating genetic analyses using the hypervariable regions of staphylococcal protein A and clumping factor B virulence genes revealed no preferential colonization of specific SA strains in persistent or intermittent carriers. Moreover, we observed that a subset of persistent and intermittent carriers retained clinically relevant community-acquired methicillin-resistant SA (CA-MRSA) strains in their nares over time.ConclusionsThe findings of this study provides added perspective on the nasal carriage dynamics between strains colonizing persistent and intermittent carriers; an area currently in need of assessment given that persistent carriers are at greater risk of autoinfection than intermittent carriers.

Mucosa of the anterior human nares can harbor Staphylococcus aureus (SA), an etiologic agent that causes severe infections. Nasal carriage of SA is a complex host-pathogen interaction involving bacterial and host mediators that influence innate host defenses. We have revealed that the exoproteome of SA nasal carrier strains contains unique determinants, which enable SA to colonize the nares. In the current study, we assess how one of these bacterial mediators, Staphylococcal protein A (Spa), affects host innate immune response to SA nasal carriage. Functional disruption of spa was performed in an SA nasal carrier strain using Targetron insertion of a group II intron. Subsequent in vitro growth kinetics analysis and ex vivo culture on human nasal epithelial cells (HNECs) revealed no differences between wild type and spa-disrupted (Δspa) SA strains. However, the Δspa mutant induced lower expression of pro-inflammatory cytokines including IL6, IL8 and TNFα from HNECs compared to the levels elicited by the wild type strain. Additionally, IL17, a crucial regulator of mucosal immunity, was induced at significantly lower levels in HNECs inoculated with Δspa SA compared to those inoculated with the wild type SA strain. Furthermore, expression of the chemokines MIP1β and MCP1, as well as HL60 neutrophil migration, were significantly reduced in conditioned media from HNECs inoculated with Δspa mutants. Spa is likely involved in mediating the mucosal response to SA colonizing the nose.