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On-person adaptive evolution of Staphylococcus aureus during atopic dermatitis increases disease severity

Felix M. Key, Veda D. Khadka, Carolina Romo-González, Kimbria J. Blake, Liwen Deng, Tucker C. Lynn, Jean C. Lee, Isaac M. Chiu, Maria Teresa García-Romero, Tami D. Lieberman

Preprint posted on 24 March 2021 https://www.biorxiv.org/content/10.1101/2021.03.24.436824v1

Opening a Time Capsule – Within-Host Evolution of Disease-Associated Staphylococcus aureus

Selected by Connor Rosen

Background:

Microbes residing on or in human tissue are subjected to a variety of evolutionary pressures, including competitive interactions with other microbes, adaptation to novel tissue microenvironments, and immunological defenses from the host. These challenges can drive genetic adaptation along multiple paths, which may enhance bacterial survival by a variety of mechanisms. However, as the bacteria adapt to pressures from one axis, their interactions with the host organism may change in unexpected ways. Given the range of diseases in which tissue-resident microbes have been implicated, it is important to understand how bacterial mutations influence disease phenotypes over time within both individual patients and the broader patient population. In this preprint, Key et al explore within-host evolution of Staphylococcus aureus in children with atopic dermatitis (AD). S. aureus can colonize the nasal passages of healthy individuals, but spreads to inflamed skin in AD and can exacerbate disease. The analysis by Key et al identifies patterns of colonization and evolution as well as a common gene target of adaptive evolution that drives disease severity.

 

Key findings:

  • This study deeply characterizes the colonization and evolution patterns of aureus in AD patients. Most patients are colonized by one single lineage of S. aureus, and even those colonized by multiple lineages show one dominant lineage. These lineages likely arose from major sweeps, where new mutations rapidly spread and replaced the full S. aureus population across multiple body sites.
  • Within one patient, multiple independent mutations arose in the capD gene, involved in synthesis of the protective polysaccharide capsule. Additional truncating mutations in capD were observed in five other patients. Such parallel evolution events can be strong indicators of adaptive evolution in microbiome studies, and indeed capD mutants showed increased colonization in a mouse AD model, along with enhanced disease. Re-examination of previously sequenced aureus genomes revealed an enrichment for capD truncations in AD isolates compared to S. aureus isolates from healthy individuals or from other infections, reinforcing the conclusions that capsule loss leads to an increasingly infective phenotype that can exacerbate AD.

 

Importance:

This work is an excellent in-depth exploration of the genetic variability and evolution of S. aureus in a population where S. aureus colonization is strongly implicated in disease pathogenesis. The clarification of the intra- and inter-individual diversity, mutational rates, and lineage sweeps is crucial for understanding the dynamic contributions of bacterial phenotypes to human disease. Additionally, the recurrent loss of capsular polysaccharide within atopic dermatitis suggests specific roles for S. aureus in the disease, highlighting the potential role for direct interactions between adhesins and host molecules or cells in enhancing S. aureus colonization and disease severity. These findings may lead to novel targeted or microbiome-based treatments for S. aureus-exacerbated AD.

 

Moving forward / Questions for authors:

  • How might pressures from other microbes influence the rate and nature of aureus evolution? For instance, it is possible that alterations in the capsule may expose S. aureus to antimicrobial products from other Staphylococcus species, as has been suggested for secreted proteases, antibiotics, or even quorum sensing peptides of the agr system (also found to be recurrently mutated in AD). Does the presence or absence of these other species, and their associated “weapons”, enable a different trajectory of S. aureus evolution in AD? There are many possible interesting interactions between the broader ecology and individual evolutionary trajectories of human-associated microbes in disease, and this work will be critical for understanding those!
  • What features might result in the single-lineage dominance of aureus populations? Different species have different propensities for monocolonization vs oligocolonization (one or several co-existing dominant lineages) in the human microbiome. Is there a clear reason why S. aureus might show more lineage restriction than other species, such as S. epidermidis, which has been suggested to exist in multiple sub-lineages derived from distinct founders?
  • The observation of capsule loss (capD truncation, Fig. 4b) in “other infections” is intriguing, as it appears to be at or above the rate observed in healthy individuals. A naïve prediction would be that in other infections, capsule loss would be disfavored due to the increase in susceptibility to immune targeting. Does this suggest any interesting features of pathogenic activity of aureus, such as that opportunistic pathogenic strains “pre-evolved” on the skin to lose capsule for enhanced colonization before transition to other tissues? Are there other functions of the S. aureus capsule that might explain this unexpected loss of function in other infections?

 

Posted on: 20 April 2021 , updated on: 21 April 2021

doi: https://doi.org/10.1242/prelights.28423

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