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Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline

Based on its important role in last-line therapeutics against multidrug-resistant bacteria, tigecycline has been increasingly important in treating infections. However, mounting reports on tigecycline-resistant bacterial strains isolated from different sources are of concern, and molecular mechanism...

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Autores principales: Li, Tao, Shan, Min, He, Jing, Wang, Xiaolan, Wang, Shaohui, Tian, Mingxing, Qi, Jingjing, Luo, Tingrong, Shi, Yonghong, Ding, Chan, Yu, Shengqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722508/
https://www.ncbi.nlm.nih.gov/pubmed/29228556
http://dx.doi.org/10.18632/oncotarget.19633
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author Li, Tao
Shan, Min
He, Jing
Wang, Xiaolan
Wang, Shaohui
Tian, Mingxing
Qi, Jingjing
Luo, Tingrong
Shi, Yonghong
Ding, Chan
Yu, Shengqing
author_facet Li, Tao
Shan, Min
He, Jing
Wang, Xiaolan
Wang, Shaohui
Tian, Mingxing
Qi, Jingjing
Luo, Tingrong
Shi, Yonghong
Ding, Chan
Yu, Shengqing
author_sort Li, Tao
collection PubMed
description Based on its important role in last-line therapeutics against multidrug-resistant bacteria, tigecycline has been increasingly important in treating infections. However, mounting reports on tigecycline-resistant bacterial strains isolated from different sources are of concern, and molecular mechanisms regarding tigecycline resistance are poorly understood. Riemerella anatipestifer is a Gram-negative, non-motile, non-spore-forming, rod-shaped bacterium, which causes fibrinous pericarditis, perihepatitis, and meningitis in infected ducks. We previously constructed a random transposon mutant library using Riemerella anatipestifer strain CH3, in present study, we described that Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline. Using the minimum inhibitory concentration assay, a mutant strain showed significantly increased (about six-fold) tigecycline susceptibility. Subsequently, the knocked-down gene was identified as M949_0459, a putative flavin adenine dinucleotide-dependent oxidoreductase. To confirm the resistance function, M949_0459 gene was overexpressed in Escherichia coli strain BL21, and the minimum inhibitory concentration analysis showed that the gene product conferred resistance to tigecycline. Additionally, expression of the M949_0459 gene under treatment with tigecycline was measured with quantitative real-time PCR. Results showed that the mRNA expression of M949_0459 gene was elevated under tigecycline treatment with dose range of 1-10 mg/L, and peaked at 4 mg/L. Moreover, two kinds of efflux pump inhibitors, carbonyl cyanide m-chlorophenyl hydrazone and phenylalanine arginyl β-naphthylamide were tested, which showed no function on tigecycline resistance in the strain CH3. Our results may provide insights into molecular mechanisms for chemotherapy in combating Riemerella anatipestifer infections.
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spelling pubmed-57225082017-12-10 Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline Li, Tao Shan, Min He, Jing Wang, Xiaolan Wang, Shaohui Tian, Mingxing Qi, Jingjing Luo, Tingrong Shi, Yonghong Ding, Chan Yu, Shengqing Oncotarget Research Paper: Pathology Based on its important role in last-line therapeutics against multidrug-resistant bacteria, tigecycline has been increasingly important in treating infections. However, mounting reports on tigecycline-resistant bacterial strains isolated from different sources are of concern, and molecular mechanisms regarding tigecycline resistance are poorly understood. Riemerella anatipestifer is a Gram-negative, non-motile, non-spore-forming, rod-shaped bacterium, which causes fibrinous pericarditis, perihepatitis, and meningitis in infected ducks. We previously constructed a random transposon mutant library using Riemerella anatipestifer strain CH3, in present study, we described that Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline. Using the minimum inhibitory concentration assay, a mutant strain showed significantly increased (about six-fold) tigecycline susceptibility. Subsequently, the knocked-down gene was identified as M949_0459, a putative flavin adenine dinucleotide-dependent oxidoreductase. To confirm the resistance function, M949_0459 gene was overexpressed in Escherichia coli strain BL21, and the minimum inhibitory concentration analysis showed that the gene product conferred resistance to tigecycline. Additionally, expression of the M949_0459 gene under treatment with tigecycline was measured with quantitative real-time PCR. Results showed that the mRNA expression of M949_0459 gene was elevated under tigecycline treatment with dose range of 1-10 mg/L, and peaked at 4 mg/L. Moreover, two kinds of efflux pump inhibitors, carbonyl cyanide m-chlorophenyl hydrazone and phenylalanine arginyl β-naphthylamide were tested, which showed no function on tigecycline resistance in the strain CH3. Our results may provide insights into molecular mechanisms for chemotherapy in combating Riemerella anatipestifer infections. Impact Journals LLC 2017-07-27 /pmc/articles/PMC5722508/ /pubmed/29228556 http://dx.doi.org/10.18632/oncotarget.19633 Text en Copyright: © 2017 Li et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper: Pathology
Li, Tao
Shan, Min
He, Jing
Wang, Xiaolan
Wang, Shaohui
Tian, Mingxing
Qi, Jingjing
Luo, Tingrong
Shi, Yonghong
Ding, Chan
Yu, Shengqing
Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline
title Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline
title_full Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline
title_fullStr Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline
title_full_unstemmed Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline
title_short Riemerella anatipestifer M949_0459 gene is responsible for the bacterial resistance to tigecycline
title_sort riemerella anatipestifer m949_0459 gene is responsible for the bacterial resistance to tigecycline
topic Research Paper: Pathology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722508/
https://www.ncbi.nlm.nih.gov/pubmed/29228556
http://dx.doi.org/10.18632/oncotarget.19633
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