{"doi":"10.1002/ctm2.828","title":"Microbial manipulation in atopic dermatitis","abstract":"Staphylococcus aureus is a Gram-positive bacteria found on the skin of approximately 20–30% of healthy subjects, but on 30–100% of patients with atopic dermatitis (AD).1 Recent reviews2, 3 have eloquently detailed a myriad of S. aureus-secreted toxins, enzymes, and cell-surface-associated antigens which contribute to AD pathogenesis (Figure 1). 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 Additionally, secreted δ-toxin promotes mast cell degranulation via phosphoinositide 3-kinase (PI3K) and Ca2+ influx-dependent mechanisms.4 Staphylococcus aureus enterotoxins and toxic shock syndrome toxin can influence disease in many ways such as: acting as superantigens, promoting clonal T-expansion and inflammatory cytokine 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.2-4 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 Recent reviews2, 3 have eloquently detailed a myriad of S. aureus-secreted toxins, enzymes, and cell-surface-associated antigens which contribute to AD pathogenesis (Figure 1). 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 Additionally, secreted δ-toxin promotes mast cell degranulation via phosphoinositide 3-kinase (PI3K) and Ca2+ influx-dependent mechanisms.4 Staphylococcus aureus enterotoxins and toxic shock syndrome toxin can influence disease in many ways such as: acting as superantigens, promoting clonal T-expansion and inflammatory cytokine 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.2-4 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). The best studied is Staphylococcus epidermidis, which was first postulated to support host production of vitamin D through basal activation of TLR2.5 Additionally, S. epidermidis induces host ceramides through the production of sphingomyelinase6 and directly inhibits S. aureus growth and colonization through induction","journal":"Clinical and Translational Medicine","year":2022,"id":267062,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":791853,"name":"Muhammad Bilal Khalid","orcid":"0000-0002-4396-9984","position":1,"is_corresponding":false},{"id":582735,"name":"Stella Hartono","orcid":"0000-0002-2276-113X","position":2,"is_corresponding":false},{"id":237344,"name":"Ian A. Myles","orcid":"0000-0001-9316-3703","position":3,"is_corresponding":false},{"id":237343,"name":"Portia Gough","orcid":"0000-0003-0201-7597","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T00:27:02.050512Z","pmid":"35452188","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}