Abstract
Many chronic infections involve bacterial biofilms, which are difficult to eliminate using conventional antibiotic treatments. Biofilm formation is a result of dynamic intra- or inter-species interactions. However, the nature of molecular interactions between bacteria in multi-species biofilms are not well understood compared to those in single-species biofilms. This study investigated the ability of probiotic Escherichia coli Nissle 1917 (EcN) to outcompete the biofilm formation of pathogens including enterohemorrhagic E. coli (EHEC), Pseudomonas aeruginosa, Staphylococcus aureus, and S. epidermidis. When dual-species biofilms were formed, EcN inhibited the EHEC biofilm population by 14-fold compared to EHEC single-species biofilms. This figure was 1,100-fold for S. aureus and 8,300-fold for S. epidermidis; however, EcN did not inhibit P. aeruginosa biofilms. In contrast, commensal E. coli did not exhibit any inhibitory effect toward other bacterial biofilms. We identified that EcN secretes DegP, a bifunctional (protease and chaperone) periplasmic protein, outside the cells and controls other biofilms. Although three E. coli strains tested in this study expressed degP, only the EcN strain secreted DegP outside the cells. The deletion of degP disabled the activity of EcN in inhibiting EHEC biofilms, and purified DegP directly repressed EHEC biofilm formation. Hence, probiotic E. coli outcompetes pathogenic biofilms via extracellular DegP activity during dual-species biofilm formation.
Highlights
The majority of biofilm studies have examined single-species cultures[5], several notable studies have investigated mixed species interactions
We chose a minimal medium with 0.4% glucose (M9G) to determine sufficient biofilm formation and inhibition in our biofilm study because a limited nutrient supply resulted in the formation of robust enterohemorrhagic E. coli (EHEC) biofilms compared to that in a rich medium (Supplementary Fig. 1)
The reduction in EHEC biofilms due to Escherichia coli Nissle 1917 (EcN) was not caused by a decrease in cell growth because EcN did not inhibit the growth of EHEC but rather increased the planktonic EHEC density by over 13-fold in the dual culture compared to the EHEC single culture (Fig. 1C)
Summary
The majority of biofilm studies have examined single-species cultures[5], several notable studies have investigated mixed species interactions. One biofilm inhibits or eradicates another biofilm by utilizing quorum sensing signals known as autoinducers and biofilm dispersal proteins[16], interspecies-biofilm signal indole[17], and the antimicrobial peptides indolicidin and bactenecin[18] Both cooperative and competitive behaviors between bacterial species determine biofilm formation dynamics in mixed bacterial communities. When EcN colonizes on the surface of the intestine together with many intestinal microorganisms including probiotic, non-probiotic, and pathogenic bacteria, EcN stimulates intestinal epithelial cells to produce human β-defensin 2 This improves host immune response[24], promotes the secretion of microcins as strain-specific antimicrobials[25], and inhibits the growth and biofilm formation of the other E. coli strains[26,27]. We identified that extracellular DegP secreted from EcN represses other biofilms
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