Abstract
The formation of biofilms is a developmental process initiated by planktonic cells transitioning to the surface, which comes full circle when cells disperse from the biofilm and transition to the planktonic mode of growth. Considering that pyruvate has been previously demonstrated to be required for the formation of P. aeruginosa biofilms, we asked whether pyruvate likewise contributes to the maintenance of the biofilm structure, with depletion of pyruvate resulting in dispersion. Here, we demonstrate that the enzymatic depletion of pyruvate coincided with the dispersion of established biofilms by S. aureus and laboratory and clinical P. aeruginosa isolates. The dispersion response was dependent on pyruvate fermentation pathway components but independent of proteins previously described to contribute to P. aeruginosa biofilm dispersion. Using porcine second-degree burn wounds infected with P. aeruginosa biofilm cells, we furthermore demonstrated that pyruvate depletion resulted in a reduction of biofilm biomass in vivo. Pyruvate-depleting conditions enhanced the efficacy of tobramycin killing of the resident wound biofilms by up to 5-logs. Our findings strongly suggest the management of pyruvate availability to be a promising strategy to combat biofilm-related infections by two principal pathogens associated with wound and cystic fibrosis lung infections.
Highlights
Biofilms are defined as a structured community of bacterial cells enclosed in a self-produced polymeric matrix and adherent to inert or living surfaces[1]
pyruvate dehydrogenase (PDH) treatment coincided with a significant loss in the crystal violet (CV)-stainable biofilm biomass, with exposure to 5 mU resulting in a 2.2-fold reduction in the biofilm biomass while exposure to 10 and 20 mU resulted on average in a 2.9-fold reduction (Fig. 1A)
Considering that established biofilms must cope with reductive stress in a similar manner to cells transitioning to the surface associated mode of growth, we asked whether pyruvate is required for the maintenance of the biofilm structure, with the enzymatic depletion of pyruvate from established biofilms resulting in biofilm cells reverting to the planktonic mode of growth
Summary
Biofilms are defined as a structured community of bacterial cells enclosed in a self-produced polymeric matrix and adherent to inert or living surfaces[1]. The finding suggested that transition to and from the surface coincides with major changes in the recalcitrance of bacterial cells to antimicrobial agents and immune cells[23,26] It is not surprising that manipulation of the biofilm developmental life cycle, attachment and dispersion, has been suggested to be a promising avenue open for biofilm control. Given the role of pyruvate in coping with the stressful, oxygen-limiting but electron-rich conditions that are prevalent in established biofilms, and that factors affecting the formation of biofilms have been shown to induce dispersion, we asked whether pyruvate-depleting conditions prevent biofilms from forming and induce biofilms to disperse
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