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Review
. 2020 Aug 11;8(8):1222.
doi: 10.3390/microorganisms8081222.

Targeting Biofilms Therapy: Current Research Strategies and Development Hurdles

Affiliations
Review

Targeting Biofilms Therapy: Current Research Strategies and Development Hurdles

Yu Jiang et al. Microorganisms. .

Abstract

Biofilms are aggregate of microorganisms in which cells are frequently embedded within a self-produced matrix of extracellular polymeric substance (EPS) and adhere to each other and/or to a surface. The development of biofilm affords pathogens significantly increased tolerances to antibiotics and antimicrobials. Up to 80% of human bacterial infections are biofilm-associated. Dispersal of biofilms can turn microbial cells into their more vulnerable planktonic phenotype and improve the therapeutic effect of antimicrobials. In this review, we focus on multiple therapeutic strategies that are currently being developed to target important structural and functional characteristics and drug resistance mechanisms of biofilms. We thoroughly discuss the current biofilm targeting strategies from four major aspects-targeting EPS, dispersal molecules, targeting quorum sensing, and targeting dormant cells. We explain each aspect with examples and discuss the main hurdles in the development of biofilm dispersal agents in order to provide a rationale for multi-targeted therapy strategies that target the complicated biofilms. Biofilm dispersal is a promising research direction to treat biofilm-associated infections in the future, and more in vivo experiments should be performed to ensure the efficacy of these therapeutic agents before being used in clinic.

Keywords: AMP; EPS; antibodies; biofilm; enzyme; metabolic; microbial resistance; quorum sensing.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Figures

Figure 1
Figure 1
Four stages of biofilm formation: (a). “initial adhesion”—microorganisms bind to host or medical device surfaces through cell surface associated adhesins; (b). “early biofilm formation”—cells begin to divide and produce extracellular polymeric substance (EPS) to enhance adhesion, while form matrix that embeds the cells; (c). “biofilm maturation”—EPS matrix develops 3-D structures which is multi-functional and protective, allowing heterogeneous chemical and physical microenvironments to be formed where microorganisms co-exist within polymicrobial and social interactions; (d). “dispersal”—cells leave the biofilm, returning to the planktonic phase. Therapeutic interventions at each stage of the biofilm development. Supplemented and modified based on Figure 1 provided in [7]. Biofilms can be targeted at each stage. (a). For example, the initial phase of biofilm formation can be disrupted by breaking the interactions between microorganisms and surface, through targeting cell surface associated adhesins. (b). The early stages of biofilm development can be disrupted by inhibiting the EPS production and cellular divisions. (c). Mature biofilms can be removed by physical-mechanical approaches, degrading the EPS-matrix, targeting the pathogenic microenvironments and social interactions within polymicrobial biofilms, as well as eliminating dormant cells. (d). Induce the EPS matrix remodeling or biofilm active dispersal events.

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