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Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC)
Colibacillosis caused by avian pathogenic E. coli (APEC), is an economically important bacterial disease of poultry. APEC are a subgroup of extra intestinal pathogenic E. coli (ExPEC) and poultry are considered potential sources of foodborne ExPEC to humans. Currently, APEC infections in poultry are...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000209/ https://www.ncbi.nlm.nih.gov/pubmed/30270715 http://dx.doi.org/10.1080/21505594.2018.1528844 |
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author | Helmy, Yosra A. Deblais, Loic Kassem, Issmat I. Kathayat, Dipak Rajashekara, Gireesh |
author_facet | Helmy, Yosra A. Deblais, Loic Kassem, Issmat I. Kathayat, Dipak Rajashekara, Gireesh |
author_sort | Helmy, Yosra A. |
collection | PubMed |
description | Colibacillosis caused by avian pathogenic E. coli (APEC), is an economically important bacterial disease of poultry. APEC are a subgroup of extra intestinal pathogenic E. coli (ExPEC) and poultry are considered potential sources of foodborne ExPEC to humans. Currently, APEC infections in poultry are controlled by antibiotics and/or vaccination; however, their effect is limited due to emergence of antibiotic resistant strains and infections with heterologous serotypes. Therefore, novel approaches are needed. Here, using the bioluminescent quorum sensing (QS) autoinducer 2 (AI-2) indicator Vibrio harveyi BB170, we screened the cell free culture supernatant of APEC O78 prepared from cultures grown in the presence of 4,182 small molecules (SMs; 100 μM). A total of 69 SMs inhibited > 75% of APEC O78 AI-2 activity in the indicator bacteria. Ten SMs that showed highest AI-2 inhibition were selected for further studies. Most of these SMs inhibited the AI-2 activity of other APEC serotypes and significantly reduced APEC O78 biofilm formation and motility. Most compounds showed minimal toxicity on human intestinal cells (Caco-2), chicken macrophage (HD-11), and chicken and sheep red blood cells, and reduced APEC survival in HD-11 and THP-1 macrophages. The SMs induced no or minimal toxicity and conferred protection against APEC in wax moth larval model. SMs affected the expression of APEC O78 QS, virulence, biofilm and motility associated genes providing insight on their potential mode(s) of action. Further testing in chickens will facilitate development of these SMs as novel therapeutics to control APEC in poultry and thereby also reduce zoonotic transmission. |
format | Online Article Text |
id | pubmed-7000209 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-70002092020-02-19 Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC) Helmy, Yosra A. Deblais, Loic Kassem, Issmat I. Kathayat, Dipak Rajashekara, Gireesh Virulence Research Paper Colibacillosis caused by avian pathogenic E. coli (APEC), is an economically important bacterial disease of poultry. APEC are a subgroup of extra intestinal pathogenic E. coli (ExPEC) and poultry are considered potential sources of foodborne ExPEC to humans. Currently, APEC infections in poultry are controlled by antibiotics and/or vaccination; however, their effect is limited due to emergence of antibiotic resistant strains and infections with heterologous serotypes. Therefore, novel approaches are needed. Here, using the bioluminescent quorum sensing (QS) autoinducer 2 (AI-2) indicator Vibrio harveyi BB170, we screened the cell free culture supernatant of APEC O78 prepared from cultures grown in the presence of 4,182 small molecules (SMs; 100 μM). A total of 69 SMs inhibited > 75% of APEC O78 AI-2 activity in the indicator bacteria. Ten SMs that showed highest AI-2 inhibition were selected for further studies. Most of these SMs inhibited the AI-2 activity of other APEC serotypes and significantly reduced APEC O78 biofilm formation and motility. Most compounds showed minimal toxicity on human intestinal cells (Caco-2), chicken macrophage (HD-11), and chicken and sheep red blood cells, and reduced APEC survival in HD-11 and THP-1 macrophages. The SMs induced no or minimal toxicity and conferred protection against APEC in wax moth larval model. SMs affected the expression of APEC O78 QS, virulence, biofilm and motility associated genes providing insight on their potential mode(s) of action. Further testing in chickens will facilitate development of these SMs as novel therapeutics to control APEC in poultry and thereby also reduce zoonotic transmission. Taylor & Francis 2018-11-02 /pmc/articles/PMC7000209/ /pubmed/30270715 http://dx.doi.org/10.1080/21505594.2018.1528844 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Helmy, Yosra A. Deblais, Loic Kassem, Issmat I. Kathayat, Dipak Rajashekara, Gireesh Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC) |
title | Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC) |
title_full | Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC) |
title_fullStr | Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC) |
title_full_unstemmed | Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC) |
title_short | Novel small molecule modulators of quorum sensing in avian pathogenic Escherichia coli (APEC) |
title_sort | novel small molecule modulators of quorum sensing in avian pathogenic escherichia coli (apec) |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000209/ https://www.ncbi.nlm.nih.gov/pubmed/30270715 http://dx.doi.org/10.1080/21505594.2018.1528844 |
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