Characteristics of Staphylococcus aureus Colonization in Cutaneous T-Cell Lymphoma

Staphylococcus aureus (SA) colonization is strongly associated with cutaneous T cell lymphoma (CTCL), and often leads to fatal bacterial infections( Lindahl et al., 2021 Lindahl L.M. Iversen L. Odum N. Kilian M. Staphylococcus aureus and Antibiotics in Cutaneous T-Cell Lymphoma. Dermatology. 2021; : 1-3 Crossref PubMed Scopus (5) Google Scholar ). growing evidence suggests that Staphylococcal enterotoxins (SEs), Staphylococcal α-toxin, and lipoprotein play important roles in promoting CTCL development and progression.( Blumel et al., 2019 Blumel E. Willerslev-Olsen A. Gluud M. Lindahl L.M. Fredholm S. Nastasi C. et al. Staphylococcal alpha-toxin tilts the balance between malignant and non-malignant CD4(+) T cells in cutaneous T-cell lymphoma. Oncoimmunology. 2019; 8e1641387 Crossref PubMed Scopus (27) Google Scholar , Fujii, 2022 Fujii K. Pathogenesis of cutaneous T cell lymphoma: Involvement of Staphylococcus aureus. J Dermatol. 2022; 49: 202-209 Crossref PubMed Scopus (4) Google Scholar ) Specifically, Staphylococcal enterotoxin A (SEA) has been linked to CTCL pathogenesis by targeting multiple cell components within the tumor microenvironment, including malignant T cells, CD8+ tumor infiltrating T cells, as well as conventional CD4+ T cells.( Willerslev-Olsen et al., 2020 Willerslev-Olsen A. Buus T.B. Nastasi C. Blumel E. Gluud M. Bonefeld C.M. et al. Staphylococcus aureus enterotoxins induce FOXP3 in neoplastic T cells in Sezary syndrome. Blood Cancer J. 2020; 10: 57 Crossref PubMed Scopus (20) Google Scholar , Willerslev-Olsen et al., 2021 Willerslev-Olsen A. Gjerdrum L.M.R. Lindahl L.M. Buus T.B. Pallesen E.M.H. Gluud M. et al. Staphylococcus aureus Induces Signal Transducer and Activator of Transcription 5‒Dependent miR-155 Expression in Cutaneous T-Cell Lymphoma. J Invest Dermatol. 2021; 141: 2449-2458 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar , Willerslev-Olsen et al., 2016 Willerslev-Olsen A. Krejsgaard T. Lindahl L.M. Litvinov I.V. Fredholm S. Petersen D.L. et al. Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma. Blood. 2016; 127: 1287-1296 Crossref PubMed Scopus (77) Google Scholar ) However, recent studies employing high-throughput sequencing have yielded conflicting results regarding the clinical significance of SA colonization in CTCL. These studies showed equal levels of SA on lesional and non-lesional skin in CTCL patients.( Salava et al., 2020 Salava A. Deptula P. Lyyski A. Laine P. Paulin L. Vakeva L. et al. Skin microbiome in cutaneous T cell lymphoma by 16S and whole genome shotgun sequencing. J Invest Dermatol. 2020; Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar , Zhang et al., 2022 Zhang Y. Seminario-Vidal L. Cohen L. Hussaini M. Yao J. Rutenberg D. et al. Alterations in the Skin Microbiota Are Associated With Symptom Severity in Mycosis Fungoides. Front Cell Infect Microbiol. 2022; 12850509 Google Scholar ) These results challenged the clinical significance of SA colonization in CTCL. High-throughput sequencing is a sensitive technique useful for detecting the DNA of skin microbiome, whereas it is insufficient in examing the viability and function of the microbiota. Therefore, our aim is to combine high-throughput sequencing with bacteriological culture and enterotoxin detection to determine the characteristics of SE-producing SA colonization in CTCL patients.