Folliculotropic Mycosis Fungoides: Current Guidance and Experience from Clinical Practice.

Introduction: Folliculotropic mycosis fungoides (FMF) is the most frequent variant of mycosis fungoides (MF), with clinical features which differ from the classic form. As for therapeutic options, the latest guidelines on MF agree on a stage-driven strategy, in consideration of clinical presentation, symptom burden and patient's comorbidities. Materials and Methods: A search on MEDLINE, PubMed, Scopus and Cochrane Library was conducted to gather the latest evidence on FMF clinical management. Manuscripts published in the last five years (January 2017-April 2022) were included. Our single-center experience was also described. Results: A total of 15 articles were analyzed, with a total of 432 patients (disease stage from IA to IVA2). The most widely-used treatment was psoralen ultra-violet A (PUVA) in monotherapy or in association with other drugs. Oral retinoid-based therapy was also described as a therapeutic option alone or in combination. Other therapy reported were based on Brentuximab Vedotin, Mogamulizumab, Carmustine, topical steroids, tazarotene and excimer laser, interferon, nitrogen mustard, imiquimod, systemic chemotherapy, extracorporeal photopheresis and stem cell transplantation. Discussion: FMF is characterized by specific clinical-pathologic features. Advanced forms assume characteristics more similar to classic MF (infiltrated plaques and nodules), whilst early stages can present in a wide range of clinical forms (acneiform lesions, follicular-like keratoses, erythematous patches). As for therapeutic options, in absence of specific guidelines, a high number of treatments are described in clinical practice, with variable results. Phototherapy in all its forms, especially as PUVA, appears to have the greatest initial therapeutic success. Retinoids, although widely used, appear to be poorly effective in monotherapy, particularly acitretin. Combination treatment with phototherapy seems to be advisable. Ionizing treatments, such as radiotherapy and TSEBT, appear effective, at least in the short term. Overall, an integrated approach is mandatory for the inconstant course of the disease and its multidisciplinary nature.

Biogenic iron-silver nanoparticles inhibit bacterial biofilm formation due to Ag+ release as determined by a novel phycoerythrin-based assay.

Silver nanoparticles (Ag-NPs) can be considered as a cost-effective alternative to antibiotics. In the presence of Fe(III)-citrate and Ag+, Klebsiella oxytoca DSM 29614 produces biogenic Ag-NPs embedded in its peculiar exopolysaccharide (EPS). K. oxytoca DSM 29614 was cultivated in a defined growth medium-containing citrate (as sole carbon source) and supplemented with Ag+ and either low or high Fe(III) concentration. As inferred from elemental analysis, transmission and scanning electron microscopy, Fourier transform infrared spectrometry and dynamic light scattering, Ag-EPS NPs were produced in both conditions and contained also Fe. The production yield of high-Fe/Ag-EPS NPs was 12 times higher than the production yield of low-Fe/Ag-EPS NPs, confirming the stimulatory effect of iron. However, relative Ag content and Ag+ ion release were higher in low-Fe/Ag-EPS NPs than in high-Fe/Ag-EPS NPs, as revealed by emission-excitation spectra by luminescent spectrometry using a novel ad hoc established phycoerythrin fluorescence-based assay. Interestingly, high and low-Fe/Ag-EPS NPs showed different and growth medium-dependent minimal inhibitory concentrations against Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 15442. In addition, low-Fe/Ag-EPS NPs exert inhibition of staphylococcal and pseudomonal biofilm formation, while high-Fe/Ag-EPS NPs inhibits staphylococcal biofilm formation only. Altogether, these results, highlighting the different capability of Ag+ release, support the idea that Fe/Ag-EPS NPs produced by K. oxytoca DSM 29614 can be considered as promising candidates in the development of specific antibacterial and anti-biofilm agents.Key points • Klebsiella oxytoca DSM 29614 produces bimetal nanoparticles containing Fe and Ag.• Fe concentration in growth medium affects nanoparticle yield and composition.• Phycoerythrin fluorescence-based assay was developed to determine Ag+release.• Antimicrobial efficacy of bimetal nanoparticle parallels Ag+ions release.

Tryptophan promotes morphological and physiological differentiation in Streptomyces coelicolor.

The molecular mechanisms regulating tryptophan biosynthesis in actinomycetes are poorly understood; similarly, the possible roles of tryptophan in the differentiation program of microorganism life-cycle are still underexplored. To unveil the possible regulatory effect of this amino acid on gene expression, an integrated study based on quantitative teverse transcription-PCR (qRT-PCR) and proteomic approaches was performed on the actinomycete model Streptomyces coelicolor. Comparative analyses on the microorganism growth in a minimal medium with or without tryptophan supplementation showed that biosynthetic trp gene expression in S. coelicolor is not subjected to a negative regulation by the presence of the end product. Conversely, tryptophan specifically induces the transcription of trp genes present in the biosynthetic gene cluster of the calcium-dependent antibiotic (CDA), a lipopeptide containing D- and L-tryptophan residues. In addition, tryptophan stimulates the transcription of the CDA gene cluster regulator cdaR and, coherently, CDA production. Surprisingly, tryptophan also promotes the production of actinorhodin, another antibiotic that does not contain this amino acid in its structure. Combined 2D-DIGE and nano liquid chromatography electrospray linear ion trap tandem mass spectrometry (LC-ESI-LIT-MS/MS) analyses revealed that tryptophan exerts a growth-stage-dependent global effect on S. coelicolor proteome, stimulating anabolic pathways and promoting the accumulation of key factors associated with morphological and physiological differentiation at the late growth stages. Phenotypic observations by scanning electron microscopy and spore production assays demonstrated an increased sporulation in the presence of tryptophan. Transcriptional analysis of catabolic genes kynA and kynB suggested that the actinomycete also uses tryptophan as a carbon and nitrogen source. In conclusion, this study originally provides the molecular basis underlying the stimulatory effect of tryptophan on the production of antibiotics and morphological development program of this actinomycete.