Enhanced Antibacterial Activity of Substituted Derivatives of NCR169C Peptide.

Medicago truncatula in symbiosis with its rhizobial bacterium partner produces more than 700 nodule-specific cysteine-rich (NCR) peptides with diverse physicochemical properties. Most of the cationic NCR peptides have antimicrobial activity and the potential to tackle antimicrobial resistance with their novel modes of action. This work focuses on the antibacterial activity of the NCR169 peptide derivatives as we previously demonstrated that the C-terminal sequence of NCR169 (NCR169C17-38) has antifungal activity, affecting the viability, morphology, and biofilm formation of various Candida species. Here, we show that NCR169C17-38 and its various substituted derivatives are also able to kill ESKAPE pathogens such as Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli. The replacement of the two cysteines with serines enhanced the antimicrobial activity against most of the tested bacteria, indicating that the formation of a disulfide bridge is not required. As tryptophan can play role in the interaction with bacterial membranes and thus in antibacterial activity, we replaced the tryptophans in the NCR169C17-38C12,17/S sequence with various modified tryptophans, namely 5-methyl tryptophan, 5-fluoro tryptophan, 6-fluoro tryptophan, 7-aza tryptophan, and 5-methoxy tryptophan, in the synthesis of NCR169C17-38C12,17/S analogs. The results demonstrate that the presence of modified fluorotryptophans can significantly enhance the antimicrobial activity without notable hemolytic effect, and this finding could be beneficial for the further development of new AMPs from the members of the NCR peptide family.

COVID-19 mortality is associated with low vitamin D levels in patients with risk factors and/or advanced age.

BACKGROUND & AIMS: Although conclusive evidence is yet lacking, it has been suggested that vitamin D deficiency (VD) may be associated with a more severe course of SARS-CoV-2 Infection (COVID-19). In this retrospective study we assessed the association of VD deficiency with mortality in a group of COVID-19 patients treated in a tertiary referral center. METHODS: Data of 257 Covid-19 patients hospitalized between 30th September 2020 and 2nd March 2021 have been collected retrospectively. The following parameters were collected: age, gender, serum level of 25-OH-Vitamin D3, outcome (survival/death), comorbidities (cancer, diabetes mellitus and chronic obstructive pulmonary disease). Serum VD measurement was done within 3 days of admission. RESULTS: VD levels were significantly lower in patients who did not survive, however, in this patients' group the average age was significantly higher than among those, who survived. After age-matching, in a subgroup of patients with risk factors and/or 60 years of age or older who survived had significantly higher VD level in their serum than those who deceased. Serum C-reactive protein, lactate-dehydrogenase and creatinin-kinase were significantly higher in the group in which the patients died, however these laboratory parameters did not correlate with the VD levels. CONCLUSION: We found that in COVID-19 infection, when old age as risk factor (60 years of age or older) was pooled with risk factors (cancer, diabetes and/or COPD), the VD levels were significantly lower in the patient group, in which the patients did not survive. We suggest further, prospective studies in similar subgroups to explore a possible causal relationship.