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

Song Lin Chua, Joey Kuok Hoong Yam, Piliang Hao, Sunil S. Adav, May Margarette Salido, Yang Liu, Michael Givskov, Siu Kwan Sze (), Tim Tolker-Nielsen and Liang Yang ()
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Song Lin Chua: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University
Joey Kuok Hoong Yam: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University
Piliang Hao: School of Biological Sciences, Nanyang Technological University
Sunil S. Adav: School of Biological Sciences, Nanyang Technological University
May Margarette Salido: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University
Yang Liu: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University
Michael Givskov: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University
Siu Kwan Sze: School of Biological Sciences, Nanyang Technological University
Tim Tolker-Nielsen: Costerton Biofilm Center, University of Copenhagen
Liang Yang: Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms10750

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