Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms

Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino ac...

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Main Authors: Chua, Song Lin, Yam, Joey Kuok Hoong, Hao, Piliang, Adav, Sunil S., Salido, May Margarette, Liu, Yang, Givskov, Michael, Sze, Siu Kwan, Tolker-Nielsen, Tim, Yang, Liang
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2017
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Online Access:https://hdl.handle.net/10356/83880
http://hdl.handle.net/10220/42860
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-838802022-02-16T16:30:27Z Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms Chua, Song Lin Yam, Joey Kuok Hoong Hao, Piliang Adav, Sunil S. Salido, May Margarette Liu, Yang Givskov, Michael Sze, Siu Kwan Tolker-Nielsen, Tim Yang, Liang School of Biological Sciences Interdisciplinary Graduate School (IGS) Singapore Centre for Environmental Life Sciences Engineering Biofilms Bacterial Infection Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a ‘last-resort’ antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections. MOE (Min. of Education, S’pore) Published version 2017-07-13T09:21:01Z 2019-12-06T15:33:46Z 2017-07-13T09:21:01Z 2019-12-06T15:33:46Z 2016 Journal Article Chua, S. L., Yam, J. K. H., Hao, P., Adav, S. S., Salido, M. M., Liu, Y., et al. (2016). Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms. Nature Communications, 7, 10750-. 2041-1723 https://hdl.handle.net/10356/83880 http://hdl.handle.net/10220/42860 10.1038/ncomms10750 26892159 en Nature Communications © 2016 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ 11 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Biofilms
Bacterial Infection
spellingShingle Biofilms
Bacterial Infection
Chua, Song Lin
Yam, Joey Kuok Hoong
Hao, Piliang
Adav, Sunil S.
Salido, May Margarette
Liu, Yang
Givskov, Michael
Sze, Siu Kwan
Tolker-Nielsen, Tim
Yang, Liang
Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
description Drug resistance and tolerance greatly diminish the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. Here we use a proteomics approach, pulsed stable isotope labelling with amino acids (pulsed-SILAC), to quantify newly expressed proteins in colistin-tolerant subpopulations of Pseudomonas aeruginosa biofilms (colistin is a ‘last-resort’ antibiotic against multidrug-resistant Gram-negative pathogens). Migration is essential for the formation of colistin-tolerant biofilm subpopulations, with colistin-tolerant cells using type IV pili to migrate onto the top of the colistin-killed biofilm. The colistin-tolerant cells employ quorum sensing (QS) to initiate the formation of new colistin-tolerant subpopulations, highlighting multicellular behaviour in antibiotic tolerance development. The macrolide erythromycin, which has been previously shown to inhibit the motility and QS of P. aeruginosa, boosts biofilm eradication by colistin. Our work provides insights on the mechanisms underlying the formation of antibiotic-tolerant populations in bacterial biofilms and indicates research avenues for designing more efficient treatments against biofilm-associated infections.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Chua, Song Lin
Yam, Joey Kuok Hoong
Hao, Piliang
Adav, Sunil S.
Salido, May Margarette
Liu, Yang
Givskov, Michael
Sze, Siu Kwan
Tolker-Nielsen, Tim
Yang, Liang
format Article
author Chua, Song Lin
Yam, Joey Kuok Hoong
Hao, Piliang
Adav, Sunil S.
Salido, May Margarette
Liu, Yang
Givskov, Michael
Sze, Siu Kwan
Tolker-Nielsen, Tim
Yang, Liang
author_sort Chua, Song Lin
title Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
title_short Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
title_full Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
title_fullStr Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
title_full_unstemmed Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms
title_sort selective labelling and eradication of antibiotic-tolerant bacterial populations in pseudomonas aeruginosa biofilms
publishDate 2017
url https://hdl.handle.net/10356/83880
http://hdl.handle.net/10220/42860
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