Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>

Drug resistance among parasitic nematodes has resulted in an urgent need for the development of new therapies. However, the high re-discovery rate of anti-nematode compounds from terrestrial environments necessitates a new repository for future drug research. Marine epiphytes are hypothesised to pro...

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Autores principales:	Nor Hawani Salikin, Malak Dubois, Jadranka Nappi, Helene Lebhar, Christopher Marquis, Suhelen Egan
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	anti-nematode anthelminthic drugs bioactives <i>Pseudoalteromonas tunicata</i> nematode <i>Caenorhabditis elegans</i> Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/81493a7ae66f4e989c8e9d16171aa009
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spelling	oai:doaj.org-article:81493a7ae66f4e989c8e9d16171aa0092021-11-25T16:49:19ZNovel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>10.3390/biomedicines91115862227-9059https://doaj.org/article/81493a7ae66f4e989c8e9d16171aa0092021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1586https://doaj.org/toc/2227-9059Drug resistance among parasitic nematodes has resulted in an urgent need for the development of new therapies. However, the high re-discovery rate of anti-nematode compounds from terrestrial environments necessitates a new repository for future drug research. Marine epiphytes are hypothesised to produce nematicidal compounds as a defence against bacterivorous predators, thus representing a promising yet underexplored source for anti-nematode drug discovery. The marine epiphytic bacterium <i>Pseudoalteromonas tunicata</i> is known to produce several bioactive compounds. Screening heterologously expressed genomic libraries of <i>P. tunicata</i> against the nematode <i>Caenorhabditis elegans</i>, identified as an <i>E. coli</i> clone (HG8), shows fast-killing activity. Here we show that clone HG8 produces a novel nematode-killing protein-1 (Nkp-1) harbouring a predicted carbohydrate-binding domain with weak homology to known bacterial pore-forming toxins. We found bacteria expressing Nkp-1 were able to colonise the <i>C. elegans</i> intestine, with exposure to both live bacteria and protein extracts resulting in physical damage and necrosis, leading to nematode death within 24 h of exposure. Furthermore, this study revealed <i>C. elegans</i> dar (deformed anal region) and internal hatching may act as a nematode defence strategy against Nkp-1 toxicity. The characterisation of this novel protein and putative mode of action not only contributes to the development of novel anti-nematode applications in the future but reaffirms the potential of marine epiphytic bacteria as a new source of novel biomolecules.Nor Hawani SalikinMalak DuboisJadranka NappiHelene LebharChristopher MarquisSuhelen EganMDPI AGarticleanti-nematodeanthelminthic drugsbioactives<i>Pseudoalteromonas tunicata</i>nematode<i>Caenorhabditis elegans</i>Biology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1586, p 1586 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	anti-nematode anthelminthic drugs bioactives <i>Pseudoalteromonas tunicata</i> nematode <i>Caenorhabditis elegans</i> Biology (General) QH301-705.5
spellingShingle	anti-nematode anthelminthic drugs bioactives <i>Pseudoalteromonas tunicata</i> nematode <i>Caenorhabditis elegans</i> Biology (General) QH301-705.5 Nor Hawani Salikin Malak Dubois Jadranka Nappi Helene Lebhar Christopher Marquis Suhelen Egan Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>
description	Drug resistance among parasitic nematodes has resulted in an urgent need for the development of new therapies. However, the high re-discovery rate of anti-nematode compounds from terrestrial environments necessitates a new repository for future drug research. Marine epiphytes are hypothesised to produce nematicidal compounds as a defence against bacterivorous predators, thus representing a promising yet underexplored source for anti-nematode drug discovery. The marine epiphytic bacterium <i>Pseudoalteromonas tunicata</i> is known to produce several bioactive compounds. Screening heterologously expressed genomic libraries of <i>P. tunicata</i> against the nematode <i>Caenorhabditis elegans</i>, identified as an <i>E. coli</i> clone (HG8), shows fast-killing activity. Here we show that clone HG8 produces a novel nematode-killing protein-1 (Nkp-1) harbouring a predicted carbohydrate-binding domain with weak homology to known bacterial pore-forming toxins. We found bacteria expressing Nkp-1 were able to colonise the <i>C. elegans</i> intestine, with exposure to both live bacteria and protein extracts resulting in physical damage and necrosis, leading to nematode death within 24 h of exposure. Furthermore, this study revealed <i>C. elegans</i> dar (deformed anal region) and internal hatching may act as a nematode defence strategy against Nkp-1 toxicity. The characterisation of this novel protein and putative mode of action not only contributes to the development of novel anti-nematode applications in the future but reaffirms the potential of marine epiphytic bacteria as a new source of novel biomolecules.
format	article
author	Nor Hawani Salikin Malak Dubois Jadranka Nappi Helene Lebhar Christopher Marquis Suhelen Egan
author_facet	Nor Hawani Salikin Malak Dubois Jadranka Nappi Helene Lebhar Christopher Marquis Suhelen Egan
author_sort	Nor Hawani Salikin
title	Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>
title_short	Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>
title_full	Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>
title_fullStr	Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>
title_full_unstemmed	Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>
title_sort	novel nematode-killing protein-1 (nkp-1) from a marine epiphytic bacterium <i>pseudoalteromonas tunicata</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/81493a7ae66f4e989c8e9d16171aa009
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Novel Nematode-Killing Protein-1 (Nkp-1) from a Marine Epiphytic Bacterium <i>Pseudoalteromonas tunicata</i>

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