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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-03-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00317/full |
| _version_ | 1828329109386690560 |
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| author | Hao eTan Lu eZhang Yuding eWeng Ronghao eChen Feng eZhu Yongxin eJin Zhihui eCheng Shouguang eJin Shouguang eJin Weihui eWu |
| author_facet | Hao eTan Lu eZhang Yuding eWeng Ronghao eChen Feng eZhu Yongxin eJin Zhihui eCheng Shouguang eJin Shouguang eJin Weihui eWu |
| author_sort | Hao eTan |
| collection | DOAJ |
| 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 (CF) 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. |
| first_indexed | 2024-04-13T20:20:03Z |
| format | Article |
| id | doaj.art-3b72980cacb149298c91a1db369c25ba |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T20:20:03Z |
| publishDate | 2016-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-3b72980cacb149298c91a1db369c25ba2022-12-22T02:31:34ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-03-01710.3389/fmicb.2016.00317182864PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosaHao eTan0Lu eZhang1Yuding eWeng2Ronghao eChen3Feng eZhu4Yongxin eJin5Zhihui eCheng6Shouguang eJin7Shouguang eJin8Weihui eWu9State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityCollege of Medicine, University of FloridaState Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Molecular Microbiology and Technology of the Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai UniversityPseudomonas 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 (CF) 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.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00317/fullAzithromycinPseudomonas aeruginosaantibiotic resistanceRNA helicaserRNA processing |
| spellingShingle | Hao eTan Lu eZhang Yuding eWeng Ronghao eChen Feng eZhu Yongxin eJin Zhihui eCheng Shouguang eJin Shouguang eJin Weihui eWu PA3297 Counteracts Antimicrobial Effects of Azithromycin in Pseudomonas aeruginosa Frontiers in Microbiology Azithromycin Pseudomonas aeruginosa antibiotic resistance RNA helicase rRNA processing |
| 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 | Azithromycin Pseudomonas aeruginosa antibiotic resistance RNA helicase rRNA processing |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.00317/full |
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