Understanding the genetic basis of resistant CTCL-related Staphylococcus aureus - a concern for individuals with mycosis fungoides

Mycosis fungoides (MF) is the most common form of cutaneous T-cell lymphoma (CTCL), a rare subtype of non-Hodgkin lymphoma. This blood cancer variety specifically affects the skin tissue causing different types of skin lesions. MF patients can be categorized into SA-positive and SA-negative groups. In the SA-positive case, the patients skin lesion is predominantly colonized by Staphylococcus aureus, leading to an abnormal skin flora. Also, SA-neutral patients exhibit an abnormal skin flora on lesions, however, these are composed of different Staphylococcus and Cutibacterium strains. After isolating different bacterial strains from MF-patients, the role of S. aureus in affecting the skin flora and the healing process of the lesions is pivotal. The aim is to determine the genetic composition and to identify different pathogenic factors in S. aureus isolates from MF patients. Indeed, a high number of pathogenic factors could be identified. Among these, genes for toxins, antibiotic resistance, antimicrobial peptides, antiseptic resistance, and proteins binding to immunoglobulins were identified. Further, for S. aureus MFMZ1 resistance towards different types of antibiotics, including reduced sensitivity to methicillin, and antimicrobial peptides was observed. The genome data disclosed an increased occurrence of octapeptide domains in the Staphylococcus Protein A (SpA) in S. aureus MFMZ1 compared to the control strain from a healthy patient, responsible for enhanced binding capacity of SpA towards host immunoglobulins. Moreover, S. aureus MFMZ1 produces a yet unidentified metabolite that may be involved in suppressing the microbiome in SA-positive patients" skin lesions.

Novel extracts from fungi were screened against S. aureus MFMZ1 to identify potential drug candidates, revealing promising agents that can inhibit either growth or biofilm formation. In conclusion, the main objective is to understand the role of staphylococci, especially, S. aureus, in MF-patients and to understand what triggers the pathogenicity of these bacteria. Here, we target first insights in the molecular basis for future treatment of S. aureus infected MF patients.