Abstract
Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. A characteristic of atopic eczema (AE) is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism. Despite this, the origins and genetic diversity of S. aureus colonizing individual patients during AE disease flares is poorly understood. To examine the microevolution of S. aureus colonization, we deep sequenced S. aureus populations from nine children with moderate to severe AE and 18 non-atopic children asymptomatically carrying S. aureus nasally. Colonization by clonal S. aureus populations was observed in both AE patients and control participants, with all but one of the individuals carrying colonies belonging to a single sequence type. Phylogenetic analysis showed that disease flares were associated with the clonal expansion of the S. aureus population, occurring over a period of weeks to months. There was a significant difference in the genetic backgrounds of S. aureus colonizing AE cases versus controls (Fisher exact test, P = 0.03). Examination of intra-host genetic heterogeneity of the colonizing S. aureus populations identified evidence of within-host selection in the AE patients, with AE variants being potentially selectively advantageous for intracellular persistence and treatment resistance.
Highlights
Clinical studies have shown a link between Staphylococcus aureus and the pathogenesis of atopic eczema (AE)
S. aureus colonization in cases and controls Nine AE patients were recruited through Ninewells Hospital in Dundee, UK, and skin swabs were obtained from five body sites, including a nostril, two areas of inflamed eczema skin, and two separate areas of clinically unaffected skin
As a measure of the relative within-host diversities of S. aureus populations, we examined the core genome of the sequenced isolates to identify single-nucleotide polymorphisms (SNPs)
Summary
Clinical studies have shown a link between Staphylococcus aureus and the pathogenesis of atopic eczema (AE). Metagenomic analysis has shown that changes in populations of microbial communities are significantly associated with disease activity in AE, and that increased in S. aureus is linked to increasing severity. Deep-sequencing studies of S. aureus populations have shown heterogeneity arising within the host and the impact on the disease-causing potential of the population (Azarian et al, 2016; Paterson et al, 2015; Young et al, 2012). By using whole-genome sequencing to genetically characterize bacteria, it is possible to investigate how populations differentiate and adapt within a host during colonization and to reconstruct the evolutionary events shaping populations (Didelot et al, 2016). We deep sequenced S. aureus populations from children with AE, enabling us to investigate the microevolution of colonization during disease flare. We have uncovered evidence of selection enriching for colonization by S. aureus of specific genetic backgrounds, as well as genetic diversification promoting the survival and persistence of these strains during colonization of AE patients
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