Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus

Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in vitro activities of thirteen AMPs (S5, S52, S6, S61, S62, S63, K...

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Autores principales:	Phantitra Sudadech, Sittiruk Roytrakul, Orawee Kaewprasert, Auttawit Sirichoat, Ploenchan Chetchotisakd, Sakawrat Kanthawong, Kiatichai Faksri
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/063d36d245df467ebbe56aea267830bf
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spelling	oai:doaj.org-article:063d36d245df467ebbe56aea267830bf2021-11-25T05:54:27ZAssessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus1932-6203https://doaj.org/article/063d36d245df467ebbe56aea267830bf2021-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8592419/?tool=EBIhttps://doaj.org/toc/1932-6203Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in vitro activities of thirteen AMPs (S5, S52, S6, S61, S62, S63, KLK, KLK1, KLK2, Pug-1, Pug-2, Pug-3 and Pug-4) that have never been investigated against drug resistant Mab isolates. Only four novel modified AMPs (S61, S62, S63 and KLK1) provided the lowest minimum inhibitory concentration (MIC) values ranging from 200–400 μg/ml against the Mab ATCC19977 strain. These four potential AMPs were further tested with 16 clinical isolates of clarithromycin resistant Mab. The majority of the tested strains (10/16 isolates, 62.5%) showed ~99% kill by all four AMPs within 24 hours with an MIC <50 μg/ml. Only two isolates (12.5%) with acquired clarithromycin resistance, however, exhibited values <50 μg/ml of four potential AMPs, S61, S62, S63 and KLK1 after 3-days-incubation. At the MICs level, S63 showed the lowest toxicity with 1.50% hemolysis and 100% PBMC viability whereas KLK1 showed the highest hemolysis (10.21%) and lowest PBMC viability (93.52%). S61, S62 and S63 were further tested with clarithromycin-AMP interaction assays and found that 5/10 (50%) of selected isolates exhibited a synergistic interaction with 0.02–0.41 FICI values. This present study demonstrated the potential application of novel AMPs as an adjunctive treatment with clarithromycin against drug resistant Mab infection.Phantitra SudadechSittiruk RoytrakulOrawee KaewprasertAuttawit SirichoatPloenchan ChetchotisakdSakawrat KanthawongKiatichai FaksriPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Phantitra Sudadech Sittiruk Roytrakul Orawee Kaewprasert Auttawit Sirichoat Ploenchan Chetchotisakd Sakawrat Kanthawong Kiatichai Faksri Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus
description	Mycobacterium abscessus (Mab) is one of the most drug resistant bacteria with a high treatment failure rate. Antimicrobial peptides (AMPs) are alternative therapeutic agents against this infection. This study was aimed to assess the in vitro activities of thirteen AMPs (S5, S52, S6, S61, S62, S63, KLK, KLK1, KLK2, Pug-1, Pug-2, Pug-3 and Pug-4) that have never been investigated against drug resistant Mab isolates. Only four novel modified AMPs (S61, S62, S63 and KLK1) provided the lowest minimum inhibitory concentration (MIC) values ranging from 200–400 μg/ml against the Mab ATCC19977 strain. These four potential AMPs were further tested with 16 clinical isolates of clarithromycin resistant Mab. The majority of the tested strains (10/16 isolates, 62.5%) showed ~99% kill by all four AMPs within 24 hours with an MIC <50 μg/ml. Only two isolates (12.5%) with acquired clarithromycin resistance, however, exhibited values <50 μg/ml of four potential AMPs, S61, S62, S63 and KLK1 after 3-days-incubation. At the MICs level, S63 showed the lowest toxicity with 1.50% hemolysis and 100% PBMC viability whereas KLK1 showed the highest hemolysis (10.21%) and lowest PBMC viability (93.52%). S61, S62 and S63 were further tested with clarithromycin-AMP interaction assays and found that 5/10 (50%) of selected isolates exhibited a synergistic interaction with 0.02–0.41 FICI values. This present study demonstrated the potential application of novel AMPs as an adjunctive treatment with clarithromycin against drug resistant Mab infection.
format	article
author	Phantitra Sudadech Sittiruk Roytrakul Orawee Kaewprasert Auttawit Sirichoat Ploenchan Chetchotisakd Sakawrat Kanthawong Kiatichai Faksri
author_facet	Phantitra Sudadech Sittiruk Roytrakul Orawee Kaewprasert Auttawit Sirichoat Ploenchan Chetchotisakd Sakawrat Kanthawong Kiatichai Faksri
author_sort	Phantitra Sudadech
title	Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus
title_short	Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus
title_full	Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus
title_fullStr	Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus
title_full_unstemmed	Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus
title_sort	assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant mycobacterium abscessus
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/063d36d245df467ebbe56aea267830bf
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Assessment of in vitro activities of novel modified antimicrobial peptides against clarithromycin resistant Mycobacterium abscessus

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