Human KS-30

The human cathelicidin hCAP18/LL-37 is an antimicrobial protein consisting of a conserved N-terminal prosequence called the cathelin-like domain and a C-terminal peptide called LL-37. This peptide contains 37 amino acid residues, and several truncated variants obtained from natural sources or by chemical synthesis differ in their capability to damage Gram positive and Gram negative bacteria as well as Candida albicans. KR-12 is the shortest peptide (12 amino acids) of LL-37 that has conserved antibacterial activity. In addition to LL-37, other active cathelicidin-derived peptides have been reported; for instance, the peptides KR-20, a 20-aa derivative of LL-37, and KS-30, a 30-aa derivative of LL-37, have been found in human sweat. Both peptides exhibit an overall increased antibacterial and antifungal activity when compared with LL-37. We investigated the effect of LL-37 and three peptides derived from this antimicrobial molecule, KR-12, KR-20 and KS-30, on the integrity of Entamoeba histolytica trophozoites. The four peptides showed effects on E. histolytica integrity and viability in the concentration range of 10-50 μM. The peptides KR-12, KR-20, KS-30 and LL-37 differed in their capability to damage the parasite integrity, with KR-20 being the most effective and with KR-12 and LL-37 being less active. These results demonstrate the ability of antimicrobial peptides derived from human cathelicidin to damage Entamoeba trophozoites. Moreover, it was shown that the integrity of the peptides is altered in the presence of an ameba soluble fraction with cysteine protease activity.

Background: Kaposi sarcoma (KS) age-standardized incidence rate is below 0.3 per 100,000 in Nordic countries. Data on KS in Finland have been sparse. Methods: A retrospective review of all the patients with KS cases managed in the Helsinki University Central Hospital between 2006 and 2018. Results: Forty patients (median age at diagnosis 45 years, 38 males) were included. About 2.5 new cases were diagnosed per year (incidence 0.16 /100,000). The different subtypes of KS were: human immunodeficiency virus (HIV) (65%), classical KS (30%), and immunodepression (5%). Patients with HIV were significantly younger, more likely to have cutaneous lesions of the face, the trunk, and mucosal lesions, and KS within lymph nodes and inner organs. KS was diagnosed at the same time as HIV in 77% of cases, 28% with CD4-cell level above 300 cells/mm3 . Among the patients with classical KS (n = 12), 75% were of Finnish origin, 41% had a second primary malignancy diagnosed, and 25% had noninsulin dependent diabetes mellitus. Among HIV patients, 27% had another AIDS-related illness, 7% of the patients developed lymphoproliferative disorders, and 7% a hemophagocytic syndrome. Patients with HIV were always treated with antiviral therapy, with pegylated liposomal doxorubicin in 57% of the cases. Local radiotherapy was the main treatment for other KS types. None of the 5 deaths during follow-up was related to KS. Conclusions: Classical KS (KS-CLA) occurs among native Finns, frequently with other present malignancies. Screening of HIV and other malignancies is warranted in new cases of KS.

Acinetobacter baumannii infections are difficult to treat due to multidrug resistance. Biofilm formation by A. baumannii is an additional factor in its ability to resist antimicrobial therapy. The antibacterial and antibiofilm activities of the human antimicrobial peptide LL-37 and its fragments KS-30, KR-20 and KR-12 against clinical isolates of multidrug-resistant (MDR) A. baumannii were evaluated. The minimal inhibitory concentration (MIC) of LL-37 against MDR A. baumannii isolates ranged from 16 to 32 μg/mL. The MIC of KS-30 fragment varied from 8.0 to 16 μg/mL and the KR-20 fragment MIC ranged from 16 to 64 μg/mL. LL-37 and KS-30 fragment exhibited 100% bactericidal activity against five A. baumannii strains, including four MDR clinical isolates, within 30 min at concentrations of 0.25-1 μg/mL. By 0.5h, the fragments KR-20 and KR-12 eliminated all tested strains at 8 and 64 μg/mL respectively. LL-37 and its fragments displayed anti-adherence activities between 32-128 μg/mL. A minimum biofilm eradication concentration (MBEC) biofilm assay demonstrated that LL-37 inhibited and dispersed A. baumannii biofilms at 32 μg/mL respectively. Truncated fragments of LL-37 inhibited biofilms at concentrations of 64-128 μg/mL. KS-30, the truncated variant of LL-37, effectively dispersed biofilms at 64 μg/mL. At 24h, no detectable toxicity was observed at the efficacious doses when cytotoxicity assays were performed. Thus, LL-37, KS-30 and KR-20 exhibit significant antimicrobial activity against MDR A. baumannii. The prevention of biofilm formation in vitro by LL-37, KS-30 and KR-20 adds significance to their efficacy. These peptides can be potential therapeutics against MDR A. baumannii infections.