Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens

Abstract The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobial-resistant isolates and the limited effects of current control methods. Advanced chemical technologies have made accessible a wide range of uncharacterized small molecules (SMs) with encouraging...

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Autores principales:	Loïc Deblais, Yosra A. Helmy, Dipak Kathayat, Huang-chi Huang, Sally A. Miller, Gireesh Rajashekara
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c2837957e6994cf4807ae81232688046
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spelling	oai:doaj.org-article:c2837957e6994cf4807ae812326880462021-12-02T15:07:48ZNovel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens10.1038/s41598-018-31249-02045-2322https://doaj.org/article/c2837957e6994cf4807ae812326880462018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31249-0https://doaj.org/toc/2045-2322Abstract The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobial-resistant isolates and the limited effects of current control methods. Advanced chemical technologies have made accessible a wide range of uncharacterized small molecules (SMs) with encouraging chemical properties for antimicrobial treatment. Of the 4,182 SMs screened in vitro, four cidal SMs were effective at 10 µM and higher against several serotypes, antibiotic-resistant, and biofilm embedded Salmonella enterica subsp. enterica serotype Typhimurium by altering cell membrane integrity. The four SMs displayed synergistic effects with ciprofloxacin, meropenem and cefeprime against Salmonella. Further, the SMs were not pernicious to most eukaryotic cells at 200 μM and cleared internalized Salmonella in infected Caco-2, HD11, and THP-1 cells at 6.25 µM and higher. The SMs also increased the longevity of Salmonella-infected Galleria mellonella larvae and reduced the population of internalized S almonella Typhimurium. Two of the SMs (SM4 and SM5) also reduced S. Typhimurium load in infected chicken ceca as well as its systemic translocation into other tissues, with minimal impact on the cecal microbiota. This study demonstrated that SMs are a viable source of potential antimicrobials applicable in food animal production against Salmonella.Loïc DeblaisYosra A. HelmyDipak KathayatHuang-chi HuangSally A. MillerGireesh RajashekaraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-17 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Loïc Deblais Yosra A. Helmy Dipak Kathayat Huang-chi Huang Sally A. Miller Gireesh Rajashekara Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens
description	Abstract The control of Salmonella from farm to fork is challenging due to the emergence of antimicrobial-resistant isolates and the limited effects of current control methods. Advanced chemical technologies have made accessible a wide range of uncharacterized small molecules (SMs) with encouraging chemical properties for antimicrobial treatment. Of the 4,182 SMs screened in vitro, four cidal SMs were effective at 10 µM and higher against several serotypes, antibiotic-resistant, and biofilm embedded Salmonella enterica subsp. enterica serotype Typhimurium by altering cell membrane integrity. The four SMs displayed synergistic effects with ciprofloxacin, meropenem and cefeprime against Salmonella. Further, the SMs were not pernicious to most eukaryotic cells at 200 μM and cleared internalized Salmonella in infected Caco-2, HD11, and THP-1 cells at 6.25 µM and higher. The SMs also increased the longevity of Salmonella-infected Galleria mellonella larvae and reduced the population of internalized S almonella Typhimurium. Two of the SMs (SM4 and SM5) also reduced S. Typhimurium load in infected chicken ceca as well as its systemic translocation into other tissues, with minimal impact on the cecal microbiota. This study demonstrated that SMs are a viable source of potential antimicrobials applicable in food animal production against Salmonella.
format	article
author	Loïc Deblais Yosra A. Helmy Dipak Kathayat Huang-chi Huang Sally A. Miller Gireesh Rajashekara
author_facet	Loïc Deblais Yosra A. Helmy Dipak Kathayat Huang-chi Huang Sally A. Miller Gireesh Rajashekara
author_sort	Loïc Deblais
title	Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens
title_short	Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens
title_full	Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens
title_fullStr	Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens
title_full_unstemmed	Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens
title_sort	novel imidazole and methoxybenzylamine growth inhibitors affecting salmonella cell envelope integrity and its persistence in chickens
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/c2837957e6994cf4807ae81232688046
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Novel Imidazole and Methoxybenzylamine Growth Inhibitors Affecting Salmonella Cell Envelope Integrity and its Persistence in Chickens

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