Genomic epidemiology and phenotypic characterization of Staphylococcus aureus isolated from atopic dermatitis patients in South China

Abstract

Atopic dermatitis (AD) is a multifactorial, chronic relapsing disease. Staphylococcus aureus is the key microbial factor in AD, linked to disease activity. However, there is limited knowledge of genomic prevalence characteristics and phenotypic features of S. aureus in AD patients in China. We investigated 108 S. aureus of AD in China and globally publicly available genome sequences of 579 S. aureus of AD. Sequence type (ST) 7, ST15 and ST188 were the major lineages in China. Genes esaC, esxB, and sea were only detected in ST7, potentially contributing to its prevalence in AD. ST188 exhibited high virulence and adhesion, possibly due to the cna gene. Phylogenetic and population structure analysis revealed that 579 strains of global AD were classified into 15 sequence clusters (SCs), with SC5, SC2, and SC7 dominating. S. aureus of Chinese AD patients was mainly distributed in SC2, SC7, and SC12. Comparative genomic highlighted genes linked to AD, including enterotoxins (seh, selk, selq, entH), adhesion genes (fnbA, fnbB, sdrD, map, fib, narH). From China and global perspectives, we analyzed S. aureus's genomic epidemic traits, phylogeny, and population structure in AD skin. These findings contribute to understanding S. aureus-host interactions and genomic diversity in AD.

Keywords: Staphylococcus aureus; Atopic dermatitis; PGWAS; Phylogenetic analysis; Whole-genome sequencing.

Fig. 1

Phylogenetic analysis and patterns of the presence of virulence factor genes (VFGs) and antimicrobial resistance genes (ARGs). Maximum likelihood (ML) tree showing the phylogenetic structure of 108 S. aureus isolates from atopic dermatitis (AD). The ML tree was constructed based on the core-genome alignment of 36,744 SNP sites. AMR, antimicrobial resistance.

Fig. 2

Comparison of major STs of S. aureus isolates. (A) Differentiated VFGs in major STs. (B) Adhesion of S. aureus to human immortalized keratinocytes (HaCaTs). Colony counts of adhesive and internalized bacteria on/in HaCaT cells after infection. n = 3. The statistical significance was measured by the one-way analysis of variance (ANOVA). (C) Kaplan–Meier survival plots of G. mellonella larvae infected with major STs of S. aureus. Larvae were injected with 10⁴ CFU of S. aureus. Survival was analysed by Kaplan–Meier survival plots and the log-rank test. Log-rank test results are as follows: Newman and ST7: P = 0.5157, Newman and ST15: P = 0.0055, Newman and ST188: P = 0.0003, ST7 and ST15: P = 0.0004, ST7 and ST188: P < 0.0001, ST15 and ST188: P = 0.2127. Data are shown from 3 independent experiments using 10 larvae per group for each S. aureus.

Fig. 3

Phylogenetic analysis and population structure of 579 S. aureus isolated from AD patients. Maximum likelihood phylogeny of 579 S. aureus isolated from AD patients is constructed on the whole-genome alignment of 92035 cgSNP sites. Pie plots represent the source distribution of isolates for each SC. Dominant multilocus sequence typing types for each SC are labelled. SC sequence cluster.

Fig. 4

Comparative genomic analysis of S. aureus between AD patients and healthy controls. (A) Comparison of the proportion of different ST types in S. aureus. (B) Comparison of the proportion of VFGs in S. aureus. (C) Comparison of the proportion of ARGs in S. aureus. The statistical significance was measured by the chi-square test.

Fig. 5

Pan-genome-wide analysis results of accessory gene for S. aureus isolates from AD and HC. Volcano plot of different accessory genes between AD and HC. The y-axis represents the -log10 (Benjamini_H_p) values derived from the genome-wide association analysis. The x-axis represents the accessory gene prevalence in AD minus the accessory gene prevalence in HC. Blue dots indicate differential genes with higher prevalence in HC. Red dots indicate differential genes with higher prevalence in AD. P value was adjusted using the Benjamini-Hochberg method.