A rare loss-of-function genetic mutation suggest a role of dermcidin deficiency in hidradenitis suppurativa pathogenesis.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a multifactorial aetiology that involves a strict interplay between genetic factors, immune dysregulation and lifestyle. Familial forms represent around 40% of total HS cases and show an autosomal dominant mode of inheritance of the disease. In this study, we conducted a whole-exome sequence analysis on an Italian family of 4 members encompassing a vertical transmission of HS. Focusing on rare damaging variants, we identified a rare insertion of one nucleotide (c.225dupA:p.A76Sfs*21) in the DCD gene encoding for the antimicrobial peptide dermcidin (DCD) that was shared by the proband, his affected father and his 11-years old daughter. Since several transcriptome studies have shown a significantly decreased expression of DCD in HS skin, we hypothesised that the identified frameshift insertion was a loss-of-function mutation that might be associated with HS susceptibility in this family. We thus confirmed by mass spectrometry that DCD levels were diminished in the affected members and showed that the antimicrobial activity of a synthetic DCD peptide resulting from the frameshift mutation was impaired. In order to define the consequences related to a decrease in DCD activity, skin microbiome analyses of different body sites were performed by comparing DCD mutant and wild type samples, and results highlighted significant differences between the groins of mutated and wild type groups. Starting from genetic analysis conducted on an HS family, our findings showed, confirming previous transcriptome results, the potential role of the antimicrobial DCD peptide as an actor playing a crucial part in the etio-pathogenesis of HS and in the maintenance of the skin's physiological microbiome composition; so, we can hypothesise that DCD could be used as a novel target for personalised therapeutic approach.

Plant Antimicrobial Peptides as Potential Tool for Topic Treatment of Hidradenitis Suppurativa.

Among chronic skin autoinflammatory diseases, Hidradenitis Suppurativa (HS) stands out for its chronicity, highly variable condition, and profound impact on the patients' quality of life. HS is characterized by suppurative skin lesions in diverse body areas, including deep-seated painful nodules, abscesses, draining sinus, and bridged scars, among others, with typical topography. To date, HS is considered a refractory disease and medical treatments aim to reduce the incidence, the infection, and the pain of the lesions. For this purpose, different classes of drugs, including anti-inflammatory molecules, antibiotics and biological drugs are being used. Antimicrobial peptides (AMPs), also called defense peptides, emerge as a new class of therapeutic compounds, with broad-spectrum antimicrobial action, in addition to reports on their anti-inflammatory, healing, and immunomodulating activity. Such peptides are present in prokaryotes and eukaryotes, as part of the innate eukaryotic immune system. It has been proposed that a deregulation in the expression of AMPs in human epithelial tissues of HS patients may be associated with the etiology of this skin disease. In this scenario, plant AMPs stand out for their richness, diversity of types, and broad antimicrobial effects, with potential application for topical systemic use in patients affected by HS.

Plant Antimicrobial Peptides: State of the Art, In Silico Prediction and Perspectives in the Omics Era.

Even before the perception or interaction with pathogens, plants rely on constitutively guardian molecules, often specific to tissue or stage, with further expression after contact with the pathogen. These guardians include small molecules as antimicrobial peptides (AMPs), generally cysteine-rich, functioning to prevent pathogen establishment. Some of these AMPs are shared among eukaryotes (eg, defensins and cyclotides), others are plant specific (eg, snakins), while some are specific to certain plant families (such as heveins). When compared with other organisms, plants tend to present a higher amount of AMP isoforms due to gene duplications or polyploidy, an occurrence possibly also associated with the sessile habit of plants, which prevents them from evading biotic and environmental stresses. Therefore, plants arise as a rich resource for new AMPs. As these molecules are difficult to retrieve from databases using simple sequence alignments, a description of their characteristics and in silico (bioinformatics) approaches used to retrieve them is provided, considering resources and databases available. The possibilities and applications based on tools versus database approaches are considerable and have been so far underestimated.