Novel antimicrobial peptides identified in legume plant, Medicago truncatula.

One of the major issues in healthcare today is antibiotic resistance. Antimicrobial peptides (AMPs), a subclass of host defense peptides, have been suggested as a viable solution for the multidrug resistance problem. Legume plants express more than 700 nodule-specific cysteine-rich (NCR) peptides. Three NCR peptides (NCR094, NCR888, and NCR992) were predicted to have antimicrobial activity using in silico AMP prediction programs. This study focused on investigating the roles of the NCRs in antimicrobial activity and antibiofilm activity, followed by in vitro toxicity profiling. Different variants were synthesized, i.e., mutated and truncated derivatives. The effect on the growth of Klebsiella pneumoniae and methicillin-resistant Staphylococcus aureus (MRSA) was monitored post-treatment, and survived cells were counted using an in vitro and ex vivo killing assay. The antibiofilm assay was conducted using subinhibitory concentrations of the NCRs and monitoring K. pneumoniae biomass, followed by crystal violet staining. The cytotoxicity profile was evaluated using erythrocyte hemolysis and leukemia (K562) cell line toxicity assays. Out of the NCRs, NCR094 and NCR992 displayed mainly in vitro and ex vivo bactericidal activity on K. pneumoniae. NCR094 wild type (WT) and NCR992 eradicated K. pneumoniae at different potency; NCR094 and NCR992 killed K. pneumoniae completely at 25 and 50 µM, respectively. However, both peptides in the wild type showed negligible bactericidal effect on MRSA in vitro and ex vivo. NCR094 and its derivatives relatively retained the antimicrobial activity on K. pneumoniae in vitro and ex vivo. NCR992 WT lost its antimicrobial activity on K. pneumoniae ex vivo, yet the different truncated and mutated variants retained some of the antimicrobial role ex vivo. All the different variants of NCR094 had no effect on MRSA in vitro and ex vivo. Similarly, NCR992's variants had a negligible bactericidal role on MRSA in vitro, yet the truncated variants had a significantly high bactericidal effect on MRSA ex vivo. NCR094.3 (cystine replacement variant) and NCR992.1 displayed significant antibiofilm activity more than 90%. NCR992.3 and NCR992.2 displayed more than 50% of antibiofilm activity. All the NCR094 forms had no toxicity, except NCR094.1 (49.38%, SD ± 3.46) and all NCR992 forms (63%-93%), which were above the cutoff (20%). Only NCR992.2 showed low toxicity on K562 (24.8%, SD ± 3.40), yet above the 20% cutoff. This study provided preliminary antimicrobial and safety data for the potential use of these peptides for therapeutical applications.IMPORTANCEThe discovery of new antibiotics is urgently needed, given the global expansion of antibiotic-resistant bacteria and the rising mortality rate. One of the initial lines of defense against microbial infections is antimicrobial peptides (AMPs). Plants can express hundreds of such AMPs as defensins and defensin-like peptides. The nodule-specific cysteine-rich (NCR) peptides are a class of defensin-like peptides that have evolved in rhizobial-legume symbioses. This study screened the antimicrobial activity of a subset of NCR sequences using online computational AMP prediction algorithms. Two novel NCRs, NCR094 and NCR992, with different variants were identified to exhibit antimicrobial activity with various potency on two problematic pathogens, K. pneumoniae and MRSA, using in vitro and ex vivo killing assays. Yet, one variant, NCR094.3, had no toxicity toward human cells and displayed antibiofilm activity, which make it a promising lead for antimicrobial drug development.

Generalized Pustular Psoriasis Induced by Infliximab in a Patient With Inflammatory Bowel Disease.

The incidence of anti-tumour necrosis factor (TNF)-induced psoriasiform eruptions has ranged in the literature between 0.5% and 10.9% of patients with inflammatory bowel disease (IBD). The morphology of the rash varies, with plaque psoriasis being the most common form. Generalized pustular eruption is reported in 10.2% of cases of anti-TNF-induced psoriasis. We are reporting a unique case of anti-TNF-associated psoriasiform eruption due to the severity of the rash presenting as a generalized pustular eruption in association with plaque psoriasiform rash requiring systemic therapy.

The Contribution of Malodour in Quality of Life of Patients With Hidradenitis Suppurativa.

BACKGROUND: Malodourous discharge in patients with hidradenitis suppurativa (HS) has a strong psychosocial impact and is often reported as a source of embarrassment, low self-esteem, social stigma, and barriers to interpersonal relationships. Malodour is a maker of bacterial colonization, and its role in HS is understudied. OBJECTIVES: The aim of this study is to assess the relationship between severity of malodourous discharge and quality-of-life impairment in patients with HS. METHODS: This is a cross-sectional study of 51 patients recruited from the Women's College Hospital and the York Dermatology Centre. Quality of life was assessed using both the Dermatology Life Quality Index (DLQI) and the Skindex-29 instruments. RESULTS: Severity of odour significantly predicts the total Skindex score after controlling for disease severity as measured by the Hurley stage and Sartorius score ( R2 = 0.39, F = 8.11, P < .0001). However, odour severity is not a predictor of DLQI ( R2 = 0.17, F = 2.63, P = .064). There was no difference in mean DLQI scores for the low- vs high-odour groups, but patients with high odour had a greater quality of life impairment as measured by the Skindex tool ( t = -4.19, df = 43, P < .0001, mean difference = -18.87). CONCLUSION: Malodour is a common symptom that significantly impairs quality of life in patients with HS. The fact that this effect is captured in Skindex and not the DLQI may be attributed to the nonspecificity of the DLQI in terms of unique disease characteristics. It is important to address odour in the management of patients with HS.

Peristomal skin complications: what dermatologists need to know.

A stoma is an artificial opening to the skin formed when a part of the gastrointestinal tract is resected and opened to the skin in order to divert the bowel content to the skin surface. The incidence of stomal and peristomal complication varies from 30 to 67% with a significant negative impact on patient quality of life. Despite their prevalence, care providers tend to show insufficient awareness of peristomal skin complications, and research-based evidence related to peristomal skin complication and management options particularly in dermatology literature is sparse. This article will present a comprehensive review of peristomal skin complications in classification, clinical presentation, causes, prevention, and management aiming at increasing knowledge about this topic.