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Lipidated Analogs of the LL-37-Derived Peptide Fragment KR12-Structural Analysis, Surface-Active Properties and Antimicrobial Activity.

ABSTRACT: An increasing number of multidrug-resistant pathogens is a serious problem of modern medicine and new antibiotics are highly demanded. In this study, different n-alkyl acids (C2-C14) and aromatic acids (benzoic and trans-cinnamic) were conjugated to the N-terminus of KR12 amide. The effect of this modification on antimicrobial activity (ESKAPE bacteria and biofilm of Staphylococcus aureus) and cytotoxicity (human red blood cells and HaCaT cell line) was examined. The effect of lipophilic modifications on helicity was studied by CD spectroscopy, whereas peptide self-assembly was studied by surface tension measurements and NMR spectroscopy. As shown, conjugation of the KR12-NH2 peptide with C4-C14 fatty acid chains enhanced the antimicrobial activity with an optimum demonstrated by C8-KR12-NH2 (MIC 1-4 ?g/mL against ESKAPE strains; MBEC of S. aureus 4-16 ?g/mL). Correlation between antimicrobial activity and self-assembly behavior of C14-KR12-NH2 and C8-KR12-NH2 has shown that the former self-assembled into larger aggregated structures, which reduced its antimicrobial activity. In conclusion, N-terminal modification can enhance antimicrobial activity of KR12-NH2; however, at the same time, the cytotoxicity increases. It seems that the selectivity against pathogens over human cells can be achieved through conjugation of peptide N-terminus with appropriate n-alkyl fatty and aromatic acids.

SUBMITTER: Kamysz E

PROVIDER: S-EPMC7036753 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Lipidated Analogs of the LL-37-Derived Peptide Fragment KR12-Structural Analysis, Surface-Active Properties and Antimicrobial Activity.

Kamysz Elżbieta E Sikorska Emilia E Jaśkiewicz Maciej M Bauer Marta M Neubauer Damian D Bartoszewska Sylwia S Barańska-Rybak Wioletta W Kamysz Wojciech W

International journal of molecular sciences 20200130 3

An increasing number of multidrug-resistant pathogens is a serious problem of modern medicine and new antibiotics are highly demanded. In this study, different n-alkyl acids (C2-C14) and aromatic acids (benzoic and trans-cinnamic) were conjugated to the N-terminus of KR12 amide. The effect of this modification on antimicrobial activity (ESKAPE bacteria and biofilm of Staphylococcus aureus) and cytotoxicity (human red blood cells and HaCaT cell line) was ...[more]

PMID: 32019109

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Project description:BackgroundVitamin D insufficiency is common in industrialized and developing nations. Recent studies have shown that vitamin D insufficiency is associated with a higher risk of active tuberculosis. Laboratory studies provided a mechanism for this link on the basis of findings that vitamin D metabolites regulate the expression of cathelicidin (LL-37), which is an endogenous antimicrobial peptide with activity against Mycobacterium tuberculosis. Little information is available on the clinical relation between vitamin D, LL-37 concentrations, and disease severity in patients with tuberculosis.ObjectiveThe primary objective of the study was to evaluate the relation between vitamin D nutriture, serum LL-37 concentrations, and tuberculosis by using samples stored in the Tuberculosis Trials Consortium serum repository.DesignWe measured 25-hydroxyvitamin D [25(OH)D] and LL-37 concentrations in 95 serum specimens from patients with culture-confirmed pulmonary tuberculosis and correlated these concentrations to clinical and demographic variables.ResultsThe prevalence of vitamin D insufficiency [serum 25(OH)D concentration lt 30 ng/mL] in patients with active tuberculosis was 86% (n = 95) with a mean baseline serum 25(OH)D concentration of 20.4 ng/mL. Factors associated with vitamin D insufficiency were black race and indoor lifestyle. The mean ( plusmn SD) baseline LL-37 concentration was 49.5 plusmn 23.8 ng/mL. Higher LL-37 concentrations correlated with acid fast bacilli sputum smear positivity and weight gt 10% below ideal body weight. Serum vitamin D status of the study subjects did not correlate with serum LL-37 concentrations.ConclusionMore prospectively designed studies are needed to evaluate the clinical implications of vitamin D insufficiency in patients with tuberculosis and the utility of circulating LL-37 as a potential biomarker in patients with active tuberculosis disease. The parent trial was registered at clinicaltrials.gov as NCT00023335.

Dataset Information

Lipidated Analogs of the LL-37-Derived Peptide Fragment KR12-Structural Analysis, Surface-Active Properties and Antimicrobial Activity.

Publications

Lipidated Analogs of the LL-37-Derived Peptide Fragment KR12-Structural Analysis, Surface-Active Properties and Antimicrobial Activity.

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