Antimicrobial Activities of LL-37 Fragment Mutant-Poly (Lactic-Co-Glycolic) Acid Conjugate against Staphylococcus aureus, Escherichia coli, and Candida albicans

Abstract

Various peptides and their derivatives have been reported to exhibit antimicrobial activities. Although these activities have been examined against microorganisms, novel methods have recently emerged for conjugation of the biomaterials to improve their activities. Here, we prepared CKR12-PLGA, in which CKR12 (a mutated fragment of human cathelicidin peptide, LL-37) was conjugated with poly (lactic-co-glycolic) acid (PLGA), and compared the antimicrobial and antifungal activities of the conjugated peptide with those of FK13 (a small fragment of LL-37) and CKR12 alone. The prepared CKR12-PLGA was characterized by dynamic light scattering and measurement of the zeta potential, critical micellar concentration, and antimicrobial activities of the fragments and conjugate. Although CKR12 showed higher antibacterial activities than FK13 against Staphylococcus aureus and Escherichia coli, the antifungal activity of CKR12 was lower than that of FK13. CKR12-PLGA showed higher antibacterial activities against S. aureus and E. coli and higher antifungal activity against Candida albicans compared to those of FK13. Additionally, CKR12-PLGA showed no hemolytic activity in erythrocytes, and scanning and transmission electron microscopy suggested that CKR12-PLGA killed and disrupted the surface structure of microbial cells. Conjugation of antimicrobial peptide fragment analogues was a successful approach for obtaining increased microbial activity with minimized cytotoxicity.

Targeted Delivery of Miconazole Employing LL37 Fragment Mutant Peptide CKR12-Poly (Lactic-Co-Glycolic) Acid Polymeric Micelles

“…The CKR12-PLGA hybrid block copolymer showed an estimated CMC value of 12 μM based on the absorbance changes reported in our previous study [ 25 ]. Therefore, the CKR12-PLGA hybrid block copolymer exhibited the behaviour of an amphiphilic block copolymer in aqueous solution and formed a micelle structure.…”

“…The procedures for synthesis and structural characterisation by Fourier transform-infrared spectroscopy, 1 H-nuclear magnetic resonance spectroscopy, and haemolytic assays of the CKR12-PLGA hybrid block copolymer have been reported previously [ 25 ].…”

“…We hypothesised that CKR12, a mutant of the antibacterial core peptide, uses a similar mechanism, as the representative human cathelicidin AMP LL-37 regulates the expression of genes encoding proteins with various functions in C. albicans [ 24 ]. This study was conducted to explore the use of a nanocarrier delivery system of micelles [ 25 ]. Miconazole (MCZ), an imidazole derivative with a broad antifungal spectrum, was used as the encapsulated sample.…”

In vitro and in vivo Activity of Phibilin Against Candida albicans

“…PI absorption assay showed that Phibilin exerts its killing effect by disrupting the integrity of the plasma membrane of C. albicans ( Figure 3 ), implying that Phibilin is a fungicidal membrane-acting AMP. Besides disrupting the cell membranes, AMPs could also disrupt the morphology of microbial cells, such as CKR12-PLGA ( Mori et al, 2021 ). However, the scanning electron microscopy showed that Phibilin had no effect on the general morphology of C. albicans cells ( Figures 4B–D ).…”

Production of a selective antibacterial fatty acid against Staphylococcus aureus by Bifidobacterium strains

“…JCM 7042 were derivatized into 4,4-Dimethyloxazoline (DMOX) and subsequently analyzed by gas chromatography-mass spectrometry (GC-MS) as described previously [35,36] . The position of the double bond of C16:1 was analyzed using the plasma-mediated modification method by liquid chromatography-mass spectrometry (LC-MS) as previously reported [37] . For LC-MS analysis, fatty acid samples were analyzed in the form of free fatty acid (FFA).…”