Bioprospecting the American Alligator (Alligator mississippiensis) Host Defense Peptidome

Bishop, Barney; Juba, Melanie L.; Devine, Megan; Barksdale, Stephanie M.; Rodriguez, Carlos A.; Chung, Myung-Jin; Russo, Paul; Vliet, Kent A.; Schnur, Joel M.; Hoek, Monique L. van

doi:10.1371/journal.pone.0117394

Cited by 47 publications

(88 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A1P was found to have stronger broad-spectrum activity than anticipated from our previous study [8]. Although A1P had weak activity against P. aeruginosa PAO1 (EC 50 = 38.6 μg/ml), it was not effective at concentrations tested against MDR P. aeruginosa (ATCC BAA-2110) (Table 4).…”

Section: Resultsmentioning

confidence: 66%

See 1 more Smart Citation

Peptides from American alligator plasma are antimicrobial against multi-drug resistant bacterial pathogens including Acinetobacter baumannii

et al. 2016

Self Cite

View full text Add to dashboard Cite

BackgroundOur group has developed a new process for isolating and identifying novel cationic antimicrobial peptides from small amounts of biological samples. Previously, we identified several active antimicrobial peptides from 100 μl of plasma from Alligator mississippiensis. These peptides were found to have in vitro antimicrobial activity against Pseudomonas aeruginosa and Staphylococcus aureus. In this work, we further characterize three of the novel peptides discovered using this process: Apo5, Apo6, and A1P.ResultsWe examined the activity of these peptides against multi-drug resistant strains and clinical isolates of common human pathogens. We investigated their structural characteristics using circular dichroism and tested for membrane disruption and DNA binding. These peptides were found to have strong in vitro activity against multi-drug resistant and clinically isolated strains of S. aureus, Escherichia coli, P. aeruginosa, and Acinetobacter baumannii. Apo5 and Apo6, peptides derived from alligator apolipoprotein C-1, depolarized the bacterial membrane. A1P, a peptide from the serpin proteinase inhibitor, did not permeabilize membranes. Performing circular dichroism analysis, Apo5 and Apo6 were found to be predominantly helical in SDS and TFE buffer, while A1P has significantly different structures in phosphate buffer, SDS, and TFE. None of these peptides were found to be hemolytic to sheep red blood cells or significantly cytotoxic up to 100 μg/ml after 24 h exposure.ConclusionsOverall, we suggest that Apo5 and Apo6 have a different mode of action than A1P, and that all three peptides make promising candidates for the treatment of drug-resistant bacteria, such as A. baumannii.

show abstract

Section: Resultsmentioning

confidence: 66%

“…It was also found that A1P had greater activity against S. aureus than P. aeruginosa [8] , indicating it may have stronger activity against Gram-positive organisms.…”

Section: Resultsmentioning

confidence: 99%

Peptides from American alligator plasma are antimicrobial against multi-drug resistant bacterial pathogens including Acinetobacter baumannii

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Apo6 is a naturally occurring (native) peptide identified intact from American alligator blood by de novo peptide mass-spectrometry sequencing [16, 17]. It is the C-terminal sequence of alligator apolipoprotein E, and was discovered using our BioProspector process [16].…”

Section: Resultsmentioning

confidence: 99%

“…Cationic antimicrobial peptides can have broad or specific activity against bacteria, viruses, or fungi and can also have host-directed immuno-modulatory functions [11, 14, 15]. Our group has been working to discover novel antimicrobial peptides from reptiles, including the American alligator ( Alligator mississippiensis ) and the Komodo dragon ( Varanus komodoensis ) [16–18]. We have discovered a number of antimicrobial peptides with strong antimicrobial activity against a range of bacteria.…”

Section: Introductionmentioning

confidence: 99%

“…We have discovered a number of antimicrobial peptides with strong antimicrobial activity against a range of bacteria. Previously, we found that peptides representing the C-terminal fragments of an apolipoprotein in A. mississippiensis had antimicrobial activity against Bacillus cereus , Escherichia coli , Pseudomonas aeruginosa , and Staphylococcus aureus , as well as drug-resistant strains of E. coli, P. aeruginosa, S. aureus , and Acinetobacter baumannii [16, 19].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Hoek

Kaushal

Bishop

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

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

show abstract

Effectiveness of Cathelicidin Antimicrobial Peptide against Ictalurid Catfish Bacterial Pathogens

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

Bioprospecting the American Alligator (Alligator mississippiensis) Host Defense Peptidome

Cited by 47 publications

References 31 publications

Peptides from American alligator plasma are antimicrobial against multi-drug resistant bacterial pathogens including Acinetobacter baumannii

Peptides from American alligator plasma are antimicrobial against multi-drug resistant bacterial pathogens including Acinetobacter baumannii

Intraperitoneal treatment with antimicrobial peptide rescues mice from a pulmonaryFrancisellainfection

Effectiveness of Cathelicidin Antimicrobial Peptide against Ictalurid Catfish Bacterial Pathogens

Contact Info

Product

Resources

About