Rational Design of RN15m4 Cathelin Domain-Based Peptides from Siamese Crocodile Cathelicidin Improves Antimicrobial Activity

Jangpromma, Nisachon; Konkchaiyaphum, Monruedee; Punpad, Arpaporn; Sosiangdi, Sirinthip; Daduang, Sakda; Klaynongsruang, Sompong; Tankrathok, Anupong

doi:10.1007/s12010-022-04210-1

Cited by 5 publications

(2 citation statements)

References 28 publications

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“…Our objective was to create peptides with a net + 4 to + 7 positive charge with 40 to 47% of hydrophobicity. The 2D structures of QL17 and its derivatives were constructed and the helical wheel projection was constructed online using the Emboss Pepwheel program 25 .…”

Section: Methodsmentioning

confidence: 99%

Rational design and characterization of cell-selective antimicrobial peptides based on a bioactive peptide from Crocodylus siamensis hemoglobin

Sosiangdi,

Taemaitree,

Tankrathok

et al. 2023

Sci Rep

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Antimicrobial resistance is a growing health concern. Antimicrobial peptides are a potential solution because they bypass conventional drug resistance mechanisms. Previously, we isolated a peptide from Crocodylus siamensis hemoglobin hydrolysate, which has antimicrobial activity and identified the main peptide from this mixture (QL17). The objective of this work was to evaluate and rationally modify QL17 in order to: (1) control its mechanism of action through bacterial membrane disruption; (2) improve its antimicrobial activity; and (3) ensure it has low cytotoxicity against normal eukaryotic cells. QL17 was rationally designed using physicochemical and template-based methods. These new peptide variants were assessed for: (1) their in vitro inhibition of microbial growth, (2) their cytotoxicity against normal cells, (3) their selectivity for microbes, and (4) the mode of action against bacteria using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and confocal microscopy. The results indicate that all designed peptides have more potent antimicrobial efficacy than QL17 and IL15 peptides. However, only the most rationally modified peptides showed strong antimicrobial activity and minimal toxicity against normal cells. In particular, IL15.3 (hydrophobicity of 47% and net charge of + 6) was a potent antimicrobial agent (MIC = 4–12 μg/mL; MBC = 6–25 μg/mL) and displayed excellent selectivity for microbes (cf. human cells) via FACS assays. Microscopy confirmed that IL15.3 acts against bacteria by disrupting the cell membrane integrity and penetrating into the membrane. This causes the release of intracellular content into the outer environment leading to the death of bacteria. Moreover, IL15.3 can also interact with DNA suggesting it could have dual mode of action. Overall, a novel variant of QL17 is described that increases antimicrobial activity by over 1000-fold (~ 5 μg/mL MIC) and has minimal cytotoxicity. It may have applications in clinical use to treat and safeguard against bacteria.

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Section: Methodsmentioning

confidence: 99%

Rational design and characterization of cell-selective antimicrobial peptides based on a bioactive peptide from Crocodylus siamensis hemoglobin

Sosiangdi,

Taemaitree,

Tankrathok

et al. 2023

Sci Rep

Self Cite

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“…The biological functions of antimicrobial peptides mainly include antibacterial, antifungal, and antiviral activities which can improve animal performance [ 11 , 12 ]. The sterilization mechanism of antimicrobial peptides mainly involves destroying the bacterial cell membrane, and thus, the development of drug resistance is difficult [ 13 , 14 ]. To kill and reduce the number of pathogenic bacteria to which animals are exposed during the breeding of livestock and poultry, antimicrobial peptides are usually added to the diet or drinking water [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of the Antimicrobial Peptide Mastoparan X on the Performance, Permeability and Microbiota Populations of Broiler Chickens

Zhu

Bai

Xia

et al. 2022

Animals

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Restrictions on antibiotics are driving the search for alternative feed additives to promote gastrointestinal health and development in broiler chicken production. Proteins including antimicrobial peptides can potentially be applied as alternatives to antibiotics and are one of the most promising alternatives. We investigated whether the addition of MPX to the diet affects the production performance, immune function and the intestinal flora of the caecal contents of broiler chickens. One hundred one-day-old chickens were randomly divided into two groups: control (basal diet) and MPX (20 mg/kg) added to the basal diet. The results indicated that dietary supplementation with MPX improved the performance and immune organ index, decreased the feed conversion ratio, increased the villus length, maintained the normal intestinal morphology and reduced the IL-6 and LITNF mRNA expression levels of inflammation-related genes. In addition, MPX increased the mRNA expression of the digestive enzymes FABP2 and SLC2A5/GLUT5 and the tight junction proteins ZO-1, Claudin-1, Occludin, JAM-2 and MUC2, maintained the intestinal permeability and regulated the intestinal morphology. Moreover, MPX increased the CAT, HMOX1 and SOD1 mRNA expression levels of the antioxidant genes. Furthermore, a 16S rRNA microflora analysis indicated that the abundance of Lactobacillus and Lactococcus in the cecum was increased after addition of MPX at 14 d and 28 d. This study explored the feasibility of using antimicrobial peptides as novel feed additives for broiler chickens and provides a theoretical basis for their application in livestock.

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A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance

Chen,

Kumar,

2023

Arch Microbiol

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Rational Design of RN15m4 Cathelin Domain-Based Peptides from Siamese Crocodile Cathelicidin Improves Antimicrobial Activity

Cited by 5 publications

References 28 publications

Rational design and characterization of cell-selective antimicrobial peptides based on a bioactive peptide from Crocodylus siamensis hemoglobin

Rational design and characterization of cell-selective antimicrobial peptides based on a bioactive peptide from Crocodylus siamensis hemoglobin

Effects of the Antimicrobial Peptide Mastoparan X on the Performance, Permeability and Microbiota Populations of Broiler Chickens

A review of current antibiotic resistance and promising antibiotics with novel modes of action to combat antibiotic resistance

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