Developing tolerance against bacteria
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It is widely accepted that pathogenic bacteria in the biofilm mode significantly contribute to the development of nosocomial infections as they are colonizing hospital settings and chronic infection sites, where they represent a serious threat to public health. Bacterial cells differentiate into several physiologically distinct subpopulations within a biofilm.
Antibiotic treatment often eradicates sensitive subpopulations, but leaves small antibiotic-tolerant subpopulations behind, resulting in recurring infections after antibiotic treatment has been stopped. Antibiotic-tolerant bacterial cells are variants of wild-type cells that can revert back to the wild type when antimicrobial treatment has ceased. Their transient nature and low abundance make it difficult to investigate their tolerance-related physiology.
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.
Researchers 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. This 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.