Evidence that Intraspecific Trait Variation among Nasal Bacteria Shapes the Distribution of Staphylococcus aureus

Abstract

b Nasal carriage of Staphylococcus aureus is a risk factor for infection, yet the bacterial determinants required for carriage are poorly defined. Interactions between S. aureus and other members of the bacterial flora may determine colonization and have been inferred in previous studies by using correlated species distributions. However, traits mediating species interactions are often polymorphic, suggesting that understanding how interactions structure communities requires a trait-based approach. We characterized S. aureus growth inhibition by the culturable bacterial aerobe consortia of 60 nasal microbiomes, and this revealed intraspecific variation in growth inhibition and that inhibitory isolates clustered within communities that were culture negative for S. aureus. Across microbiomes, the cumulative community-level growth inhibition was negatively associated with S. aureus incidence. To fully understand the ecological processes structuring microbiomes, it will be crucial to account for intraspecific variation in the traits that mediate species interactions.T he primary niche of Staphylococcus aureus is the human anterior nares, where it resides persistently in 25 to 30% of the population, while other individuals are only colonized intermittently (1). In hospital patients, carriage is a risk factor for infection (2) and is associated with recurrent disease. Preoperative topical antimicrobial treatments are known to reduce carriage of S. aureus and disease in cardiothoracic patients (3); there is evidence that other patient groups might also benefit from decolonization (4, 5, 6). Carriage rates vary with gender, age, smoking, serum glucose levels, oral contraceptive use, dialysis, addiction to drugs, and certain diseases such as atopic dermatitis (3,7,8,9,10). Fewer studies have addressed the role of the cocolonizing microbiota in S. aureus carriage. Three studies have used 16S rRNA gene sequencing to characterize nasal species distributions, and from these distributions scientists have inferred interactions at the species level (11,12,13 Yan et al. (13) confirmed the species-level interactions between S. aureus and C. accolens and C. pseudodiphthericum and proposed these as the major ecological interactions between bacteria in relation to S. aureus carriage. Moreover, their study identified variations in ecological relationships between nasal microenvironments that highlighted the dynamic complexities between bacteria across host epithelial surfaces.It is increasingly appreciated that species-level approaches are insufficient to understand the ecological factors structuring a microbiome (14, 15). The primary reason for this is that microbial species are not homogeneous with respect to many ecologically important traits, and as such, species-level analyses can underestimate the importance of ecological interactions (for a review of recent advances, see Boon et al. [16]). Further, species-level approaches give little insight into the ecological mechanisms underlying species distribution patterns. Trait-base...

Comparative Genomics of Staphylococcus Reveals Determinants of Speciation and Diversification of Antimicrobial Defense

“…In summary, we have identified differential encoding and diversity of antimicrobial resistance regulators and their associated transporters across the staphylococci. Our previous studies of the nasal microbiome correlated cumulative antimicrobial production with community structure, limitation of invasion and S. aureus exclusion (38, 39, 40). Further dissection of antimicrobial sensing and discrimination via the TCS systems BraSR and GraSR combined with analysis of their associated transport specificities will provide information that can be layered with niche-relevant antimicrobial activities from competing species.…”

Deferred Growth Inhibition Assay to Quantify the Effect of Bacteria-derived Antimicrobials on Competition

“…If the dilution is not optimal, clear measurements of inhibition may not be easily determined. This assay was optimized using various nasal isolates as inhibitor-producing strains across a wide range of Gram-positive and Gram-negative species versus S. aureus SH1000 as the competitor strain 7,8 . It has subsequently been tested using various coagulase-negative and coagulase-positive staphylococci as competitor and inhibitor-producing strains.…”

“…The technique described here can be used to assess the potential of individual strains to exclude other bacteria. This method has previously been used to show a positive correlation between the presence of Staphylococcus aureus inhibitory bacteria and the absence of S. aureus in a nasal community 7 .…”

“…It can also detect positive interactions, whereby the presence of the inhibitor strain actually improves the growth of the competitor strain. This assay can be used to create quantitative data (zone of clearing size) and qualitative data (degree of inhibition), both of which can be overlaid onto data of the presence or absence of a species within a community to find correlations between phenotype (trait) and competitive exclusion 7 .…”

Prolonged Growth of a Clinical Staphylococcus aureus Strain Selects for a Stable Small-Colony-Variant Cell Type

“…For nasal carriage, for example, there are no common genetic or phenotypic traits that define a successful colonizing S. aureus strain from one that is unable to colonize. In addition to this, there are host factors and the microbiome of the nasal passage (23,24). Certainly bacterial growth is inhibited by this combination of factors in the nasal passage, which means bacterial growth is slow.…”