Commensal–Pathogen Interactions along the Human Nasal Passages

Bacterial species that commonly reside on surfaces of the human nasal passages (Fig 1) interact with the host along a continuum from beneficial to harmful, i.e., from mutualist to commensal to pathogen. Likewise, the host responds along a continuum from tolerance to damage [1]. In fact, a small number of bacterial species that are prevalent and often abundant members of the nasal microbiota are important human pathogens, e.g., Staphylococcus aureus and Streptococcus pneumoniae. In the United States alone, S. pneumoniae contributes to ~20,000 deaths [2] and methicillin-resistant strains of S. aureus (MRSA) contribute to ~10,000 deaths annually [3]. Despite this significant mortality, most S. aureus and S. pneumoniae interactions with humans are harmless and do not result in disease, i.e., are commensal. However, benign colonization can be the starting point for disease, host–host transmission, and selection for new microbial traits. This duality of behavior from commensal to pathogen has led to the term pathobiont [4]. The factors that shift the behavior of pathobionts from a commensal to a pathogenic state remain to be identified. However, the interplay of pathobionts with other members of the microbiota might be one such factor. The combination of cultivation and 16S rRNA gene-based approaches has revealed new insights into this possibility and has sparked renewed interest in determining the molecular mechanisms of commensal–pathobiont interactions in the nasal microbiota. One goal of these efforts is to identify potentially beneficial bacteria (mutualists) that might either exclude pathobionts through colonization resistance or shift the behavior of colonizing pathobionts towards commensalism. The feasibility of this goal is supported by two studies in adult Danish twins. Data from a large study of 617 twin pairs indicate that host genetics play a limited role in determining S. aureus nostril colonization and suggest a larger role for environmental factors, which could include the microbiota [6]. In a follow-up study of 46 monozygotic and 43 dizygotic twin pairs, the bacterial composition of the nasal microbiota is also predominantly an environmentally derived phenotype with host genetics playing a minor role in composition, but a larger role in determining bacterial density on nasal surfaces [7]. These studies, along with evidence that nasal microbiota composition changes over time, including seasonal variation [8–13], support the hypothesis that nasal microbiota composition could be altered for therapeutic benefit [7,14]. This hypothesis is bolstered by reports of negative correlations in colonization between key pathobionts (e.g., S. pneumoniae and S. aureus) and select benign commensals and of alterations in microbiota composition in disease states, e.g., middle ear infections (otitis media) [7,15–26]. Such studies further highlight the need to understand the role and function of the