Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32

Pathogenic microbes are developing resistance to established antibiotics, making the development of novel antimicrobial molecules paramount. One major resource for discovery of antimicrobials is the arsenal of innate immunity molecules that are part of the first line of pathogen defense in many orga...

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Main Authors: Bomai K. Kerenga, James A. McKenna, Peta J. Harvey, Pedro Quimbar, Donovan Garcia-Ceron, Fung T. Lay, Thanh Kha Phan, Prem K. Veneer, Shaily Vasa, Kathy Parisi, Thomas M. A. Shafee, Nicole L. van der Weerden, Mark D. Hulett, David J. Craik, Marilyn A. Anderson, Mark R. Bleackley
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-04-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2019.00795/full
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author Bomai K. Kerenga
James A. McKenna
Peta J. Harvey
Pedro Quimbar
Donovan Garcia-Ceron
Fung T. Lay
Thanh Kha Phan
Prem K. Veneer
Shaily Vasa
Kathy Parisi
Thomas M. A. Shafee
Nicole L. van der Weerden
Mark D. Hulett
David J. Craik
Marilyn A. Anderson
Mark R. Bleackley
author_facet Bomai K. Kerenga
James A. McKenna
Peta J. Harvey
Pedro Quimbar
Donovan Garcia-Ceron
Fung T. Lay
Thanh Kha Phan
Prem K. Veneer
Shaily Vasa
Kathy Parisi
Thomas M. A. Shafee
Nicole L. van der Weerden
Mark D. Hulett
David J. Craik
Marilyn A. Anderson
Mark R. Bleackley
author_sort Bomai K. Kerenga
collection DOAJ
description Pathogenic microbes are developing resistance to established antibiotics, making the development of novel antimicrobial molecules paramount. One major resource for discovery of antimicrobials is the arsenal of innate immunity molecules that are part of the first line of pathogen defense in many organisms. Gene encoded cationic antimicrobial peptides are a major constituent of innate immune arsenals. Many of these peptides exhibit potent antimicrobial activity in vitro. However, a major hurdle that has impeded their development for use in the clinic is the loss of activity at physiological salt concentrations, attributed to weakening of the electrostatic interactions between the cationic peptide and anionic surfaces of the microbial cells in the presence of salt. Using plant defensins we have investigated the relationship between the charge of an antimicrobial peptide and its activity in media with elevated salt concentrations. Plant defensins are a large class of antifungal peptides that have remarkable stability at extremes of pH and temperature as well as resistance to protease digestion. A search of a database of over 1200 plant defensins identified ZmD32, a defensin from Zea mays, with a predicted charge of +10.1 at pH 7, the highest of any defensin in the database. Recombinant ZmD32 retained activity against a range of fungal species in media containing elevated concentrations of salt. In addition, ZmD32 was active against Candida albicans biofilms as well as both Gram negative and Gram-positive bacteria. This broad spectrum antimicrobial activity, combined with a low toxicity on human cells make ZmD32 an attractive lead for development of future antimicrobial molecules.
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spelling doaj.art-405411b58d674762ae65be780f160ed32022-12-22T00:51:13ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-04-011010.3389/fmicb.2019.00795455591Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32Bomai K. Kerenga0James A. McKenna1Peta J. Harvey2Pedro Quimbar3Donovan Garcia-Ceron4Fung T. Lay5Thanh Kha Phan6Prem K. Veneer7Shaily Vasa8Kathy Parisi9Thomas M. A. Shafee10Nicole L. van der Weerden11Mark D. Hulett12David J. Craik13Marilyn A. Anderson14Mark R. Bleackley15Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, AustraliaPathogenic microbes are developing resistance to established antibiotics, making the development of novel antimicrobial molecules paramount. One major resource for discovery of antimicrobials is the arsenal of innate immunity molecules that are part of the first line of pathogen defense in many organisms. Gene encoded cationic antimicrobial peptides are a major constituent of innate immune arsenals. Many of these peptides exhibit potent antimicrobial activity in vitro. However, a major hurdle that has impeded their development for use in the clinic is the loss of activity at physiological salt concentrations, attributed to weakening of the electrostatic interactions between the cationic peptide and anionic surfaces of the microbial cells in the presence of salt. Using plant defensins we have investigated the relationship between the charge of an antimicrobial peptide and its activity in media with elevated salt concentrations. Plant defensins are a large class of antifungal peptides that have remarkable stability at extremes of pH and temperature as well as resistance to protease digestion. A search of a database of over 1200 plant defensins identified ZmD32, a defensin from Zea mays, with a predicted charge of +10.1 at pH 7, the highest of any defensin in the database. Recombinant ZmD32 retained activity against a range of fungal species in media containing elevated concentrations of salt. In addition, ZmD32 was active against Candida albicans biofilms as well as both Gram negative and Gram-positive bacteria. This broad spectrum antimicrobial activity, combined with a low toxicity on human cells make ZmD32 an attractive lead for development of future antimicrobial molecules.https://www.frontiersin.org/article/10.3389/fmicb.2019.00795/fullplant defensinantifungalantibacterialsalt toleranceantimicrobial peptide
spellingShingle Bomai K. Kerenga
James A. McKenna
Peta J. Harvey
Pedro Quimbar
Donovan Garcia-Ceron
Fung T. Lay
Thanh Kha Phan
Prem K. Veneer
Shaily Vasa
Kathy Parisi
Thomas M. A. Shafee
Nicole L. van der Weerden
Mark D. Hulett
David J. Craik
Marilyn A. Anderson
Mark R. Bleackley
Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32
Frontiers in Microbiology
plant defensin
antifungal
antibacterial
salt tolerance
antimicrobial peptide
title Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32
title_full Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32
title_fullStr Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32
title_full_unstemmed Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32
title_short Salt-Tolerant Antifungal and Antibacterial Activities of the Corn Defensin ZmD32
title_sort salt tolerant antifungal and antibacterial activities of the corn defensin zmd32
topic plant defensin
antifungal
antibacterial
salt tolerance
antimicrobial peptide
url https://www.frontiersin.org/article/10.3389/fmicb.2019.00795/full
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