Proteomics

Dataset Information

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Selective labeling and eradication of antibiotic tolerant bacterial populations in pathogenic biofilms


ABSTRACT: Drug resistance and tolerance eliminate the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. To uncover antibiotic tolerance mechanisms in biofilms, we applied stable isotope labeling with amino acids (SILAC) proteomics to selectively label and compare proteomes of sensitive and tolerant subpopulations of biofilms formed by Pseudomonas aeruginosa towards colistin, a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens. Migration was essential in forming colistin-tolerant biofilm subpopulations, as colistin-tolerant cell-aggregates migrated with type IV pili, onto the top of killed biofilm. The colistin-tolerant cell-aggregates employed quorum sensing (QS) to initiate the formation of fresh colistin-tolerant subpopulations, highlighting multicellular behavior in antibiotic tolerance development. Erythromycin treatment which inhibits motility and QS, boosted biofilm eradication by colistin. This novel ‘-omics’ strategy to study antibiotic tolerant cells provides key insights for designing novel treatments against infections unsuppressed by conventional antimicrobials.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Pseudomonas aeruginosa PAO1H2O  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Sunil Adav  

LAB HEAD: Siu Kwan Sze

PROVIDER: PXD002369 | Pride | 2016-02-16

REPOSITORIES: pride

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Publications

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

Chua Song Lin SL   Yam Joey Kuok Hoong JK   Hao Piliang P   Adav Sunil S SS   Salido May Margarette MM   Liu Yang Y   Givskov Michael M   Sze Siu Kwan SK   Tolker-Nielsen Tim T   Yang Liang L  

Nature Communications 20160219


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  ...[more]

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