Updated understanding of Staphylococcus aureus in atopic dermatitis: From virulence factors to commensals and clonal complexes

Abstract

Atopic dermatitis (AD) is an inflammatory dermatosis with a pathogenesis believed to be due to a combination of genetic, immunologic and environmental factors that affects up to 5% of adults and 20% of children worldwide. 1,2 Common genetic factors include polymorphisms in the filaggrin structural protein, interleukin (IL)-4 receptor and vitamin D receptor. [3][4][5] AD is driven by multiple immune pathways, most commonly with activation of Th2 and Th22 T-cell subsets. 6 Crosstalk between commensals and the host immune system modulates adaptive and innate immune responses in AD. 7 Staphylococcus aureus (SA) in AD lesions and surrounding normal skin was first noted by Leyden et al. in the 1970s; since then, the understanding of its role in AD has drastically evolved. 8,9 SA is a well-established exacerbator of AD; it is frequently isolated from the skin of AD patients and increased SA density is found during flares. 10 A meta-analysis in 2016 reported a pooled prevalence of SA colonization among AD patients of 70% in lesional skin, 39% in non-lesional skin and 62% in the nose. 11 More recently, Kong et al 12 found that AD treatments and flares were closely associated with shifts in the cutaneous microbial diversity. While current evidence has established that SA proliferates during flares and plays a role in the cycle of epidermal breakdown and inflammation, a true causal relationship has not been established. Herein, we will summarize the

Mutual Links between the Endocannabinoidome and the Gut Microbiome, with Special Reference to Companion Animals: A Nutritional Viewpoint

“…Obesity, diabetes mellitus, cancer, cardiovascular diseases and neuroinflammatory disorders (like, for example, neuropathic pain and depression) are just a few examples of human and pet diseases with clear differences in fecal bacterial composition compared to healthy conditions [37,[50][51][52][53][54][55]. Not to mention that aside from the gut microbiome, the skin and oral microbiome are becoming increasingly involved in other human and pet disorders, such as atopic dermatitis [56,57] and periodontal diseases [58,59].…”

Microbial manipulation in atopic dermatitis

“…In brief, proteins, such as clumping factor B and fibronectin binding proteins, promote the adhesion of S. aureus to the stratum corneum. Staphylococcal Protein A can activate proinflammatory nuclear factor kappa B (NF‐κB) signaling through direct engagement of tumor necrosis factor receptor 1 (TNFR1) 2,3 . Lipoprotein and lipoteichoic acid induce TSLP in human keratinocytes via Toll‐like receptors (TLR‐) 2 and 6, 2 and phenol‐soluble modulins also induce proinflammatory cytokines in human keratinocytes 2,3 .…”

“…Staphylococcal α‐toxin not only promotes NLRP3 activation and IL‐31 production but additionally compromises the keratinocyte layer by altering E‐cadherin integrity 2–4 . Although no single virulence factor correlates with AD prevalence or severity, AD exacerbations correlate with differences in the specific combinations of virulence factors within distinct lineages of S. aureus (called clonal complexes) 3 …”

“…[2][3][4] Although no single virulence factor correlates with AD prevalence or severity, AD exacerbations correlate with differences in the specific combinations of virulence factors within distinct lineages of S. aureus (called clonal complexes). 3 While the deleterious impacts of S. aureus are well established, AD is definitively non-communicable. The realization that a non-contagious disease like AD could not be caused by a highly contagious organism like S. aureus fostered the appreciation for the protective role of other microbes in skin homeostasis (Figure 1).…”

“…MHC-II, Major Histocompatibility Complex 2; TLR2, Toll-like receptor 2; TNFR2, tumor necrosis factor receptor 2; nAChR, nicotinic acetylcholine receptor; IL-10, interleukin-10; Vit D, vitamin D. Image generated by Ian Myles using BioRender.com release; inducing IgE isotype switching in B-cells; directly activating mast cells and basophils; or stimulating secretion of itch-inducing interleukin 31 (IL-31). 2,3 Staphylococcal α-toxin not only promotes NLRP3 activation and IL-31 production but additionally compromises the keratinocyte layer by altering E-cadherin integrity. [2][3][4] Although no single virulence factor correlates with AD prevalence or severity, AD exacerbations correlate with differences in the specific combinations of virulence factors within distinct lineages of S. aureus (called clonal complexes).…”