Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>

Peptoids (oligo <i>N</i>-substituted glycines) are peptide analogues, which can be designed to mimic host antimicrobial peptides, with the advantage that they are resistant to proteolytic degradation. Few studies on the antimicrobial efficacy of peptoids have focused on Gram negative ana...

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Main Authors: Jamie Toole, Hannah L. Bolt, John J. Marley, Sheila Patrick, Steven L. Cobb, Fionnuala T. Lundy
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/16/4741
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spelling doaj-48670fe932d44af1b663638899917cb72021-08-26T14:06:56ZengMDPI AGMolecules1420-30492021-08-01264741474110.3390/molecules26164741Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>Jamie Toole0Hannah L. Bolt1John J. Marley2Sheila Patrick3Steven L. Cobb4Fionnuala T. Lundy5Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKDepartment of Chemistry, Biophysical Sciences Institute, Durham University, South Road, Durham DH1 3LE, UKDepartment of Oral Surgery, Royal Victoria Hospital, Grosvenor Road, Belfast BT12 6BA, UKWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKDepartment of Chemistry, Biophysical Sciences Institute, Durham University, South Road, Durham DH1 3LE, UKWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKPeptoids (oligo <i>N</i>-substituted glycines) are peptide analogues, which can be designed to mimic host antimicrobial peptides, with the advantage that they are resistant to proteolytic degradation. Few studies on the antimicrobial efficacy of peptoids have focused on Gram negative anaerobic microbes associated with clinical infections, which are commonly recalcitrant to antibiotic treatment. We therefore studied the cytotoxicity and antibiofilm activity of a family of peptoids against the Gram negative obligate anaerobe <i>Fusobacterium nucleatum</i>, which is associated with infections in the oral cavity. Two peptoids, peptoid <b>4</b> (NaeNpheNphe)4 and peptoid <b>9</b> (NahNspeNspe)<sub>3</sub> were shown to be efficacious against <i>F. nucleatum</i> biofilms at a concentration of 1 μM. At this concentration, peptoids <b>4</b> and <b>9</b> were not cytotoxic to human erythrocytes or primary human gingival fibroblast cells. Peptoids <b>4</b> and <b>9</b> therefore have merit as future therapeutics for the treatment of oral infections.https://www.mdpi.com/1420-3049/26/16/4741antimicrobialbiofilmscytotoxicitypeptidomimeticpeptoidtargeted therapeutic
collection DOAJ
language English
format Article
sources DOAJ
author Jamie Toole
Hannah L. Bolt
John J. Marley
Sheila Patrick
Steven L. Cobb
Fionnuala T. Lundy
spellingShingle Jamie Toole
Hannah L. Bolt
John J. Marley
Sheila Patrick
Steven L. Cobb
Fionnuala T. Lundy
Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>
Molecules
antimicrobial
biofilms
cytotoxicity
peptidomimetic
peptoid
targeted therapeutic
author_facet Jamie Toole
Hannah L. Bolt
John J. Marley
Sheila Patrick
Steven L. Cobb
Fionnuala T. Lundy
author_sort Jamie Toole
title Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>
title_short Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>
title_full Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>
title_fullStr Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>
title_full_unstemmed Peptoids with Antibiofilm Activity against the Gram Negative Obligate Anaerobe, <i>Fusobacterium nucleatum</i>
title_sort peptoids with antibiofilm activity against the gram negative obligate anaerobe, <i>fusobacterium nucleatum</i>
publisher MDPI AG
series Molecules
issn 1420-3049
publishDate 2021-08-01
description Peptoids (oligo <i>N</i>-substituted glycines) are peptide analogues, which can be designed to mimic host antimicrobial peptides, with the advantage that they are resistant to proteolytic degradation. Few studies on the antimicrobial efficacy of peptoids have focused on Gram negative anaerobic microbes associated with clinical infections, which are commonly recalcitrant to antibiotic treatment. We therefore studied the cytotoxicity and antibiofilm activity of a family of peptoids against the Gram negative obligate anaerobe <i>Fusobacterium nucleatum</i>, which is associated with infections in the oral cavity. Two peptoids, peptoid <b>4</b> (NaeNpheNphe)4 and peptoid <b>9</b> (NahNspeNspe)<sub>3</sub> were shown to be efficacious against <i>F. nucleatum</i> biofilms at a concentration of 1 μM. At this concentration, peptoids <b>4</b> and <b>9</b> were not cytotoxic to human erythrocytes or primary human gingival fibroblast cells. Peptoids <b>4</b> and <b>9</b> therefore have merit as future therapeutics for the treatment of oral infections.
topic antimicrobial
biofilms
cytotoxicity
peptidomimetic
peptoid
targeted therapeutic
url https://www.mdpi.com/1420-3049/26/16/4741
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