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Effect of Temperature on Metronidazole Resistance in Helicobacter pylori
Efficacy of Helicobacter pylori (H. pylori) eradication therapy has declined due to rapid rises in antibiotic resistance. We investigated how increased temperature affected H. pylori (NCTC 11637) growth and its sensitivity to metronidazole in vitro. We performed transcriptomic profiling using RNA-se...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170400/ https://www.ncbi.nlm.nih.gov/pubmed/34093508 http://dx.doi.org/10.3389/fmicb.2021.681911 |
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author | Gong, Meiliang Han, Yingjie Wang, Xuning Tao, Hongjin Meng, Fansen Hou, Baicun Sun, Benjamin B. Wang, Gangshi |
author_facet | Gong, Meiliang Han, Yingjie Wang, Xuning Tao, Hongjin Meng, Fansen Hou, Baicun Sun, Benjamin B. Wang, Gangshi |
author_sort | Gong, Meiliang |
collection | PubMed |
description | Efficacy of Helicobacter pylori (H. pylori) eradication therapy has declined due to rapid rises in antibiotic resistance. We investigated how increased temperature affected H. pylori (NCTC 11637) growth and its sensitivity to metronidazole in vitro. We performed transcriptomic profiling using RNA-sequencing to identify differentially expressed genes (DEGs) associated with increased temperature. Transcriptional pathways involved in temperature-driven metronidazole resistance changes were analyzed through bioinformatic and literature curation approaches. We showed that H. pylori growth was inhibited at 41°C and inhibition was more apparent with prolonged incubation. Resistance to metronidazole was also reduced—minimum inhibitory concentration for metronidazole decreased from > 256 μg/ml at 37°C to 8 μg/ml at 41°C after culturing for 3 days. RNA-sequencing results, which were highly concordant within treatment conditions, revealed more than one third of genes (583/1,552) to be differentially expressed at increased temperatures with similar proportions up and down-regulated. Quantitative real-time PCR validation for 8 out of 10 DEGs tested gave consistent direction in gene expression changes. We found enrichment for redox and oxygen radical pathways, highlighting a mechanistic pathway driving temperature-related metronidazole resistance. Independent literature review of published genes associated with metronidazole resistance revealed 46 gene candidates, 21 of which showed differential expression and 7 out of 9 DEGs associated with “redox” resistance pathways. Sanger sequencing did not detect any changes in genetic sequences for known resistance genes rdxA, frxA nor fdxB. Our findings suggest that temperature increase can inhibit the growth and reduce H. pylori resistance to metronidazole. Redox pathways are possible potential drivers in metronidazole resistance change induced by temperature. Our study provides insight into potential novel approaches in treating antibiotic resistant H. pylori. |
format | Online Article Text |
id | pubmed-8170400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81704002021-06-03 Effect of Temperature on Metronidazole Resistance in Helicobacter pylori Gong, Meiliang Han, Yingjie Wang, Xuning Tao, Hongjin Meng, Fansen Hou, Baicun Sun, Benjamin B. Wang, Gangshi Front Microbiol Microbiology Efficacy of Helicobacter pylori (H. pylori) eradication therapy has declined due to rapid rises in antibiotic resistance. We investigated how increased temperature affected H. pylori (NCTC 11637) growth and its sensitivity to metronidazole in vitro. We performed transcriptomic profiling using RNA-sequencing to identify differentially expressed genes (DEGs) associated with increased temperature. Transcriptional pathways involved in temperature-driven metronidazole resistance changes were analyzed through bioinformatic and literature curation approaches. We showed that H. pylori growth was inhibited at 41°C and inhibition was more apparent with prolonged incubation. Resistance to metronidazole was also reduced—minimum inhibitory concentration for metronidazole decreased from > 256 μg/ml at 37°C to 8 μg/ml at 41°C after culturing for 3 days. RNA-sequencing results, which were highly concordant within treatment conditions, revealed more than one third of genes (583/1,552) to be differentially expressed at increased temperatures with similar proportions up and down-regulated. Quantitative real-time PCR validation for 8 out of 10 DEGs tested gave consistent direction in gene expression changes. We found enrichment for redox and oxygen radical pathways, highlighting a mechanistic pathway driving temperature-related metronidazole resistance. Independent literature review of published genes associated with metronidazole resistance revealed 46 gene candidates, 21 of which showed differential expression and 7 out of 9 DEGs associated with “redox” resistance pathways. Sanger sequencing did not detect any changes in genetic sequences for known resistance genes rdxA, frxA nor fdxB. Our findings suggest that temperature increase can inhibit the growth and reduce H. pylori resistance to metronidazole. Redox pathways are possible potential drivers in metronidazole resistance change induced by temperature. Our study provides insight into potential novel approaches in treating antibiotic resistant H. pylori. Frontiers Media S.A. 2021-05-19 /pmc/articles/PMC8170400/ /pubmed/34093508 http://dx.doi.org/10.3389/fmicb.2021.681911 Text en Copyright © 2021 Gong, Han, Wang, Tao, Meng, Hou, Sun and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Gong, Meiliang Han, Yingjie Wang, Xuning Tao, Hongjin Meng, Fansen Hou, Baicun Sun, Benjamin B. Wang, Gangshi Effect of Temperature on Metronidazole Resistance in Helicobacter pylori |
title | Effect of Temperature on Metronidazole Resistance in Helicobacter pylori |
title_full | Effect of Temperature on Metronidazole Resistance in Helicobacter pylori |
title_fullStr | Effect of Temperature on Metronidazole Resistance in Helicobacter pylori |
title_full_unstemmed | Effect of Temperature on Metronidazole Resistance in Helicobacter pylori |
title_short | Effect of Temperature on Metronidazole Resistance in Helicobacter pylori |
title_sort | effect of temperature on metronidazole resistance in helicobacter pylori |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170400/ https://www.ncbi.nlm.nih.gov/pubmed/34093508 http://dx.doi.org/10.3389/fmicb.2021.681911 |
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