Clinical Escherichia coli: From Biofilm Formation to New Antibiofilm Strategies

Abstract

Escherichia coli is one of the species most frequently involved in biofilm-related diseases, being especially important in urinary tract infections, causing relapses or chronic infections. Compared to their planktonic analogues, biofilms confer to the bacteria the capacity to be up to 1000-fold more resistant to antibiotics and to evade the action of the host's immune system. For this reason, biofilm-related infections are very difficult to treat. To develop new strategies against biofilms, it is important to know the mechanisms involved in their formation. In this review, the different steps of biofilm formation in E. coli, the mechanisms of tolerance to antimicrobials and new compounds and strategies to combat biofilms are discussed.

Keywords: Escherichia coli; biofilms; clinical importance; non-traditional approaches; resistance.

Figure 1

Adherence: physicochemical properties such as osmolarity, ionic strength, pH, and nutrient availability, play a significant role at this stage. Reversible attachments allow bacteria to move to a new location when environmental conditions are unfavorable for their establishment. Then, bacteria suppress flagella and begin irreversible attachment to surfaces.

Figure 2

Proteins involved in flagellar synthesis in E. coli. Distribution of flagellar proteins (excluding chemotaxis proteins). Proteins transcribed by the master operon flhDC, class I genes, are shown in blue. Proteins involved in the basal body and flagellar hook, transcribed by class II genes, are shown in green. Proteins responsible for the flagellar filament and chemotactic signaling system, transcribed by class III genes, are shown in light brown. Figure adapted from the KEGG pathway database www.genome.jp/kegg/pathway/eco/eco02040.html (accessed on 25 November 2020).

Figure 3

Maturation: sessile bacteria produce the extracellular matrix of the biofilm, which protects them from adverse conditions.

Figure 4

Dispersal process. (A) Active detachment is a mechanism by which bacteria detach from biofilm in response to environmental factors. These factors cause physicochemical changes within the biofilm that lead to the escape of dispersed cells. (B) Passive detachment is a mechanism in which external factors such as human disturbances detach the biofilm.

Figure 5

Mechanisms involved in biofilm formation of E. coli are regulated by c-di-GMP and TCS. (A) c-di-GMP mediates the synthesis of PGA; (B) Synthesis of cellulose through activation of CsgD; (C) The DGCs and PDEs modulate the c-di-GMP concentrations essential for biofilm development; (D) Synthesis of curli fibres. Curli and cellulose are co-expressed via CsgD activation; (E) Flagellar activity regulates the flagellar motor by c-di-GMP; (F) The TCS CpxAR promotes PGA and inhibits curli production; (G) The RcsCDB TCS regulates colonic acid production and inhibits the flhDC master operon; (H) The EnvZ/OmpR TCS activates curli synthesis and represses flagella; (I) The csgDEFG operon is regulated at the post-transcriptional level by sRNA. Solid lines indicate positive (green arrows) and negative (red flat cap) regulatory effects. Dashed lines indicate process direction.

Figure 6

QS regulation and the Csr regulatory circuit in E. coli. (A) In early biofilm development, low amounts of AI-2 are present in the extracellular medium and LsrR represses lsr expression; (B) AI-2 is transported to the extracellular medium via YdgG, gathering large amounts of AI-2. In turn, the Pts transporter translocates the AI-2 into the cell and Lsrk phosporylates AI-2 to P-AI-2. This phosphorylation leads to de-repression of the lsr operon; (C) In the last phase, AI-2 is depleted from the extracellular medium through the PTS and LsrABCD transporter. CsrA mediates both the post-transcriptional inhibition of the luxS gene and the expression of the lsr operon. In contrast, the TCS, BarA and UrvY, regulate the transcription of the luxS gene. Solid lines indicate positive (arrows) and negative (flat cap) regulatory effects.

Figure 7

Mechanisms of antimicrobial tolerance in biofilms. (1) Low antimicrobial penetration. (2) Reduced growth rates and stress responses. (3) Persister cells. (4) Efflux pumps. (5) Horizontal gene transfer.