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

TY - JOUR

T1 - Selective labelling and eradication of antibiotic-tolerant bacterial populations in Pseudomonas aeruginosa biofilms

AU - Chua, Song Lin

AU - Yam, Joey Kuok Hoong

AU - Hao, Piliang

AU - Adav, Sunil S

AU - Salido, May Margarette

AU - Liu, Yang

AU - Givskov, Michael

AU - Sze, Siu Kwan

AU - Tolker-Nielsen, Tim

AU - Yang, Liang

PY - 2016/2/19

Y1 - 2016/2/19

N2 - 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 â €' last-resortâ 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.

AB - 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 â €' last-resortâ 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.

U2 - 10.1038/ncomms10750

DO - 10.1038/ncomms10750

M3 - Journal article

C2 - 26892159

SN - 2041-1723

VL - 7

JO - Nature Communications

JF - Nature Communications

M1 - 10750

ER -