Cathelicidin antimicrobial peptide from Alligator mississippiensis has antibacterial activity against multi-drug resistant Acinetobacter baumanii and Klebsiella pneumoniae

Barksdale, Stephanie M.; Hrifko, Evelyn J.; Hoek, Monique L. van

doi:10.1016/j.dci.2017.01.011

Cited by 60 publications

(77 citation statements)

References 69 publications

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“…We assessed the depolarization of bacterial membranes using DiSC 3 (5), a membrane potential sensitive dye, which intercalates itself in the lipid bilayer resulting in the self-quenching of the dye [38]. If depolarizing compounds are added, the potential decreases, and DiSC 3 (5) is released into the solution causing an increase in fluorescence relative to the reduction of membrane potential [31, 37, 38]. Figure 2A indicates a concentration-dependent increase in fluorescence when F. tularensis LVS was treated with two different concentrations of peptides (10 µg/ml and 1 µg/ml).…”

Section: Resultsmentioning

confidence: 99%

“…To examine whether the GATR peptides may be toxic to mammalian cells (particularly those peptides with higher charge), we performed hemolysis assays, cytotoxicity assays using the MTT assay, and toxicity experiments in G. mellonella waxworms. First, hemolysis assays using sheep red blood cells were performed at peptide concentrations of 100 µg/ml for 1 h [19, 31, 34]. GATR-5, −6, and −7 showed statistically significant hemolysis, in particular GATR-6 and GATR-7, each of which had hemolysis levels of greater than 20% of RBCs ( Figure 4A ).…”

Section: Resultsmentioning

confidence: 99%

“…GATR-5, −6, and −7 showed statistically significant hemolysis, in particular GATR-6 and GATR-7, each of which had hemolysis levels of greater than 20% of RBCs ( Figure 4A ). Next, we measured cytotoxicity of the GATR peptides by using the MTT assay as a measure of cell viability following peptide treatment [19, 31, 34]. A549 human lung epithelial cells and HepG2 liver cells were treated with 100 µg/ml peptide for 24 h. Shown in Figures 4B and 4C , some statistically significant suppression of cell proliferation was seen in A549 cells for GATR-3, GATR-6, and GATR-7; however, no peptides show statistical suppression of cell growth when tested against HepG2 cells.…”

Section: Resultsmentioning

confidence: 99%

“…The hemolysis assay was performed using washed, defibrinated sheep blood as previously described [31]. Sheep red blood cells (2% RBC) in phosphate buffered saline (PBS) were added to various dilutions of peptide reconstituted in PBS in a sterile U-bottom 96 well plate.…”

Section: Methodsmentioning

confidence: 99%

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Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Hoek

Kaushal

Bishop

et al. 2019

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7Our long-term goal is to identify new antimicrobial peptides that might be effective 8 against pneumonic Francisella infection in mice. Previously, our group searched the peptidome 9 of the American alligator for novel cationic antimicrobial peptides and identified a naturally-10 occurring C-terminal fragment of apolipoprotein C-1, which we called Apo6. This peptide was 11 found to have antibacterial activity against the ESKAPE pathogens, including those exhibiting 12 multi-drug resistance. In this work, we tested Apo6 and synthetic derivatives for antibacterial 13 activity against Francisella tularensis including the virulent strain F. tularensis SchuS4.14 Francisella is inherently highly resistant to the cyclic peptide polymyxin antibiotics and beta-15 lactam antibiotics. We found that our synthetic peptide derivatives (called GATR peptides), 16 designed with increased hydrophobicity and charge, had generally stronger in vitro antimicrobial 17 activity against Francisella than the parent peptide Apo6. The GATR peptides had a greater 18 effect on the bacterial membrane than the Apo6 peptide and were able to bind Francisella LPS, 19 suggesting their mechanism of action against Francisella. Cytotoxicity experiments showed low 20 cytotoxicity for most of the GATR peptides, and whole organism toxicity studies in the 21 waxworm allowed us to down-select to two our lead peptides, GATR-3 and GATR-6. These 22 peptides were tested in a murine pulmonary tularemia model. We found that the GATR-3 peptide 23 rescued 50-60% of mice from lethal tularemia infection when administered systemically through 24 2 the intraperitoneal route. This peptide is a candidate for further pre-clinical studies for a potential 25 peptide-based approach to tularemia. 26

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Hoek

Kaushal

Bishop

et al. 2019

Preprint

Self Cite

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“…Согласно результатам исследований Stephanie M. Barksdale [5], самым эффективным бактерицидным действием против MDR Acinetobacter baumanii и Klebsiella pneumoniae и минимальным токсическим влиянием обладает AM-CATH36 дериват кателици-дина американского аллигатора.…”

Section: кателицидин и его дериватыunclassified

Лікарські Засоби, Основою Яких Є Молекулярні Структури Антимікробних Пептидів, Та Терапевтичні Можливості В Лікуванні Інфекційних Захворювань Респіраторного Тракту (Частина 1)

Абатуров¹,

Kryuchko²,

Lezhenko³

2021

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Актуальною темою сучасних досліджень, спрямованих на пошук і розробку нових антимікробних лікарських засобів, є вивчення ендолізинів, бактеріоцинів, антимікробних пептидів, які базуються на молекулярних структурах, а також створення препаратів моноклональних антитіл, спрямованих проти бактеріальних факторів вірулентності, пробіотиків та вакцин. Антимікробні пептиди, взаємодіючи з бактеріями, призводять до деструкції бактеріальної стінки за рахунок порушення її цілісності, а саме — утворення циліндричних, тороїдальних пор або шляхом розриву внутрішньої мембрани бактеріальної стінки. Більшість антимікробних пептидів людини представлені кателіцидином і дефензинами. На даний час ведуться активні пошуки щодо створення дериватів або аналогів людських дефензинів, які можна було б використовувати як лікарські засоби при лікуванні інфекційних захворювань респіраторного тракту.

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Effectiveness of Cathelicidin Antimicrobial Peptide against Ictalurid Catfish Bacterial Pathogens

et al. 2021

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One of the major goals in aquaculture is to protect fish against infectious diseases as disease outbreaks could lead to economic losses if not controlled. Antimicrobial peptides (AMPs), a class of highly conserved peptides known to possess direct antimicrobial activities against invading pathogens, were evaluated for their ability to protect Channel Catfish Ictalurus punctatus and hybrid catfish (female Channel Catfish × male Blue Catfish I. furcatus) against infection caused by the fish pathogen Aeromonas hydrophila ML09‐119. To identify effective peptides, the minimum inhibitory concentrations against bacterial pathogens Edwardsiella ictaluri S97‐773, Edwardsiella piscicida E22‐10, A. hydrophila ML09‐119, Aeromonas veronii 03X03876, and Flavobacterium columnare GL‐001 were determined in vitro. In general and overall, cathelicidins derived from alligator and sea snake exhibited more potent and rapid antimicrobial activities against the tested catfish pathogens as compared to cecropin and pleurocidin AMPs and ampicillin, the antibiotic control. When the peptides (2.5 µg of peptide/g of fish) were injected into fish and simultaneously challenged with A. hydrophila through immersion, increased survival rates in Channel Catfish and hybrid catfish were observed in both cathelicidin (alligator and sea snake) treatments as compared to other peptides and the infected control (P < 0.001) with alligator cathelicidin being the overall best treatment. Bacterial numbers in the kidney and liver of Channel Catfish and hybrid catfish also decreased (P < 0.05) for cathelicidin‐injected groups at 24 and 48 h after challenge infection. These results show the potential of cathelicidin to protect catfish against bacterial infections and suggest that an approach overexpressing the peptide in transgenic fish, which is the long‐term goal of this research program, may provide a method of decreasing bacterial disease problems in catfish as delivering the peptides via individual injection or feeding would not be economically feasible.

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Cathelicidin antimicrobial peptide from Alligator mississippiensis has antibacterial activity against multi-drug resistant Acinetobacter baumanii and Klebsiella pneumoniae

Cited by 60 publications

References 69 publications

Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Effectiveness of Cathelicidin Antimicrobial Peptide against Ictalurid Catfish Bacterial Pathogens

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