Efflux pumps as potential targets for biofilm inhibition

Abstract

Biofilms account for a great deal of infectious diseases and contribute significantly to antimicrobial resistance. Efflux pumps confer antimicrobial resistance to microorganisms and involve multiple processes of biofilm formation. Efflux pump inhibitors (EPIs) are attracting considerable attention as a biofilm inhibition strategy. The regulatory functions of efflux pumps in biofilm formation such as mediating adherence, quorum sensing (QS) systems, and the expression of biofilm-associated genes have been increasingly identified. The versatile properties confer efflux pumps both positive and negative effects on biofilm formation. Furthermore, the expression and function of efflux pumps in biofilm formation are species-specific. Therefore, this review aims to detail the double-edged sword role of efflux pumps in biofilm formation to provide potential inhibition targets and give an overview of the effects of EPIs on biofilm formation.

Keywords: biofilm; efflux pump; efflux pump inhibitor; motility; quorum sensing.

Figure 1

Schematic representation of the four phases of biofilm formation: (A) reversible adherence to surfaces; (B) irreversible adherence and formation of microcolonies; (C) proliferation of cells and production of EPSs establishing a three-dimensional structure; (D) dispersal of planktonic cells to re-build new biofilms.

Figure 2

Schematic presentation of six families or superfamilies of multidrug efflux pumps and the energy sources: the resistance-nodulation–cell-division (RND) superfamily, the ATP-binding cassette (ABC) superfamily, the major facilitator superfamily (MFS), the multidrug and toxic compound extrusion (MATE) family, the small multidrug resistance (SMR) family, and the proteobacterial antimicrobial compound efflux (PACE) family. The ABC-type efflux pumps are energized by ATP hydrolysis, while the efflux pumps from other families are driven by the proton motive force. In Gram-negative bacteria, the RND-, ABC-, and MFS-type efflux pumps frequently form tripartite complexes comprised of inner membrane pumps, periplasmic adapter proteins, and the outer-membrane protein channel to span both the inner and outer membranes. The ABC-and MFS-type efflux pumps can also function in single-component forms. IM, inner membrane; OM, outer membrane.