Staphylococcus Aureus Mutations During Treatment for Atopic Dermatitis

This article was originally published on Dermatology Times. This version has been lightly edited.

The pathogen Staphylococcus aureus often invades the inflamed skin of people with atopic dermatitis (AD), worsening the disease by increasing skin damage.

S aureus is found on healthy skin but appears in higher numbers on diseased skin because it exploits the fragile skin barrier. Researchers sought to understand the impact of de novo microbiome mutations on diseases such as AD. Their findings were published in Cell Host and Microbe.

AD develops at different rates and severity, and although factors such as genetic differences or environmental defects in barrier function explain some of the differences in response to treatment, they do not explain them all.

To identify mutations acquired by S aureus that develop under natural selection, researchers conducted a prospective longitudinal study of 23 children aged 5 to 15 years with moderate to severe AD in Mexico. Over the course of 9 months and 5 visits, patients were prescribed standard treatments, including topical steroids, emollients, and bleach baths. 

The scoring AD (SCORAD) scale was used at each visit to assess disease severity. Swabs of healthy and affected skin were taken from 7 sites at each visit.

“From each of the 225 swabs that yielded growth resembling S aureus, we picked up to 10 single-colony isolates for subculture and sequencing, resulting in 1499 S aureus whole genomes,” the study authors wrote.

Most participants were consistently colonized by a single major lineage of S aureus. The researchers estimated the molecular clock of the lineages for 6 of the patients with the most isolates, and their results showed that AD-affected skin did not have a significant effect on S aureus mutation rates.

Over time, 2 patterns of on-person evolution were produced: diversification into long coexisting genotypes or within-lineage genotypic replacement. Study analyses suggested that within-lineage genotypic replacement of S aureus was more common on the AD skin.

Investigators theorize that the inflamed skin of patients with AD or treatments they are undergoing could contribute to an elevated mutation rate.

The researchers found, “that S aureus rapidly adapts via de novo mutations on people being treated for AD, that adaptive mutants spread across the whole body—including the nares—and that loss-of-function mutations in an S aureus gene closely associated with virulence, capD, are more frequent on the skin of people with AD than healthy controls.”

Findings support the role of on-person de novo mutation on patients with AD instead of transmission from another person. The researchers also noted mutations in capD, which could offer a survival advantage to S. aureus on AD skin. 

Reference

Key FM, Khadka VD, Romo-González C, et al. On-person adaptive evolution of Staphylococcus aureus during treatment for atopic dermatitis. Cell Host Microbe. 2023;31(4):593-603.e7. doi:10.1016/j.chom.2023.03.009 https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(23)00113-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1931312823001130%3Fshowall%3Dtrue