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PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa

Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide anti...

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Autores principales: Tan, Hao, Zhang, Lu, Weng, Yuding, Chen, Ronghao, Zhu, Feng, Jin, Yongxin, Cheng, Zhihui, Jin, Shouguang, Wu, Weihui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792872/
https://www.ncbi.nlm.nih.gov/pubmed/27014238
http://dx.doi.org/10.3389/fmicb.2016.00317
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author Tan, Hao
Zhang, Lu
Weng, Yuding
Chen, Ronghao
Zhu, Feng
Jin, Yongxin
Cheng, Zhihui
Jin, Shouguang
Wu, Weihui
author_facet Tan, Hao
Zhang, Lu
Weng, Yuding
Chen, Ronghao
Zhu, Feng
Jin, Yongxin
Cheng, Zhihui
Jin, Shouguang
Wu, Weihui
author_sort Tan, Hao
collection PubMed
description Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM) provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here, we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM.
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spelling pubmed-47928722016-03-24 PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa Tan, Hao Zhang, Lu Weng, Yuding Chen, Ronghao Zhu, Feng Jin, Yongxin Cheng, Zhihui Jin, Shouguang Wu, Weihui Front Microbiol Microbiology Pseudomonas aeruginosa causes acute and chronic infections in human. Its increasing resistance to antibiotics requires alternative treatments that are more effective than available strategies. Among the alternatives is the unconventional usage of conventional antibiotics, of which the macrolide antibiotic azithromycin (AZM) provides a paradigmatic example. AZM therapy is associated with a small but consistent improvement in respiratory function of cystic fibrosis patients suffering from chronic P. aeruginosa infection. Besides immunomodulating activities, AZM represses bacterial genes involved in virulence, quorum sensing, biofilm formation, and motility, all of which are due to stalling of ribosome and depletion of cellular tRNA pool. However, how P. aeruginosa responds to and counteracts the effects of AZM remain elusive. Here, we found that deficiency of PA3297, a gene encoding a DEAH-box helicase, intensified AZM-mediated bacterial killing, suppression of pyocyanin production and swarming motility, and hypersusceptibility to hydrogen peroxide. We demonstrated that expression of PA3297 is induced by the interaction between AZM and ribosome. Importantly, mutation of PA3297 resulted in elevated levels of unprocessed 23S-5S rRNA in the presence of AZM, which might lead to increased susceptibility to AZM-mediated effects. Our results revealed one of the bacterial responses in counteracting the detrimental effects of AZM. Frontiers Media S.A. 2016-03-16 /pmc/articles/PMC4792872/ /pubmed/27014238 http://dx.doi.org/10.3389/fmicb.2016.00317 Text en Copyright © 2016 Tan, Zhang, Weng, Chen, Zhu, Jin, Cheng, Jin and Wu. http://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) or licensor 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
Tan, Hao
Zhang, Lu
Weng, Yuding
Chen, Ronghao
Zhu, Feng
Jin, Yongxin
Cheng, Zhihui
Jin, Shouguang
Wu, Weihui
PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa
title PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa
title_full PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa
title_fullStr PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa
title_full_unstemmed PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa
title_short PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa
title_sort pa3297 counteracts antimicrobial effects of azithromycin in pseudomonas aeruginosa
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792872/
https://www.ncbi.nlm.nih.gov/pubmed/27014238
http://dx.doi.org/10.3389/fmicb.2016.00317
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