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Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens Santana, Felix L.; Estrada, Karel; Alford, Morgan A.; Wu, Bing C.; Dostert, Melanie; Pedraz, Lucas; Akhoundsadegh, Noushin; Kalsi, Pavneet; Haney, Evan F.; Straus, Suzana; Corzo, Gerardo; Hancock, R. E. W. (Robert E. W.)

Abstract

Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used to screen the genomes of four crocodylian species for encoded cathelicidins and eighteen novel sequences were identified. Synthetic cathelicidins showed broad spectrum antimicrobial and antibiofilm activity against several clinically important antibiotic-resistant bacteria. In particular, the As-CATH8 cathelicidin showed potent in vitro activity profiles similar to the last-resort antibiotics vancomycin and polymyxin B. In addition, As-CATH8 demonstrated rapid killing of planktonic and biofilm cells, which correlated with its ability to cause cytoplasmic membrane depolarization and permeabilization as well as binding to DNA. As-CATH8 displayed greater antibiofilm activity than the human cathelicidin LL-37 against methicillin-resistant Staphylococcus aureus in a human organoid model of biofilm skin infection. Furthermore, As-CATH8 demonstrated strong antibacterial effects in a murine abscess model of high-density bacterial infections against clinical isolates of S. aureus and Acinetobacter baumannii, two of the most common bacterial species causing skin infections globally. Overall, this work expands the repertoire of cathelicidin peptides known in crocodylians, including one with considerable therapeutic promise for treating common skin infections.

Item Metadata

Title
Novel Alligator Cathelicidin As-CATH8 Demonstrates Anti-Infective Activity against Clinically Relevant and Crocodylian Bacterial Pathogens
Creator
Santana, Felix L.; Estrada, Karel; Alford, Morgan A.; Wu, Bing C.; Dostert, Melanie; Pedraz, Lucas; Akhoundsadegh, Noushin; Kalsi, Pavneet; Haney, Evan F.; Straus, Suzana; Corzo, Gerardo; Hancock, R. E. W. (Robert E. W.)
Contributor
University of British Columbia. Centre for Microbial Diseases and Immunity Research
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2022-11-11
Description
Host defense peptides (HDPs) represent an alternative way to address the emergence of antibiotic resistance. Crocodylians are interesting species for the study of these molecules because of their potent immune system, which confers high resistance to infection. Profile hidden Markov models were used to screen the genomes of four crocodylian species for encoded cathelicidins and eighteen novel sequences were identified. Synthetic cathelicidins showed broad spectrum antimicrobial and antibiofilm activity against several clinically important antibiotic-resistant bacteria. In particular, the As-CATH8 cathelicidin showed potent in vitro activity profiles similar to the last-resort antibiotics vancomycin and polymyxin B. In addition, As-CATH8 demonstrated rapid killing of planktonic and biofilm cells, which correlated with its ability to cause cytoplasmic membrane depolarization and permeabilization as well as binding to DNA. As-CATH8 displayed greater antibiofilm activity than the human cathelicidin LL-37 against methicillin-resistant Staphylococcus aureus in a human organoid model of biofilm skin infection. Furthermore, As-CATH8 demonstrated strong antibacterial effects in a murine abscess model of high-density bacterial infections against clinical isolates of S. aureus and Acinetobacter baumannii, two of the most common bacterial species causing skin infections globally. Overall, this work expands the repertoire of cathelicidin peptides known in crocodylians, including one with considerable therapeutic promise for treating common skin infections.
Subject
cathelicidins; antimicrobial peptides; LL-37; biofilms; abscess model; skin model; reptiles
Genre
Article
Type
Text
Language
eng
Date Available
2023-11-30
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0437964
URI
http://hdl.handle.net/2429/86699
Affiliation
Medicine, Faculty of; Science, Faculty of; Non UBC; Chemistry, Department of; Microbiology and Immunology, Department of
Citation
Antibiotics 11 (11): 1603 (2022)
Publisher DOI
10.3390/antibiotics11111603
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher; Postdoctoral; Graduate
Rights URI
https://creativecommons.org/licenses/by/4.0/
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CC BY 4.0