New Perspectives on the Use of Phytochemicals as an Emergent Strategy to Control Bacterial Infections Including Biofilms

Abstract

The majority of current infectious diseases are almost untreatable by conventional antibiotic therapy given the advent of multidrug-resistant bacteria. The degree of severity and the persistence of infections are worsened when microorganisms form biofilms. Therefore, efforts are being applied to develop new drugs not as vulnerable as the current ones to bacterial resistance mechanisms, and also able to target bacteria in biofilms. Natural products, especially those obtained from plants, have proven to be outstanding compounds with unique properties, making them perfect candidates for these much-needed therapeutics. This review presents the current knowledge on the potentialities of plant products as antibiotic adjuvants to restore the therapeutic activity of drugs. Further, the difficulties associated with the use of the existing antibiotics in the treatment of biofilm-related infections are described. To counteract the biofilm resistance problems, innovative strategies are suggested based on literature data. Among the proposed strategies, the use of phytochemicals to inhibit or eradicate biofilms is highlighted. An overview on the use of phytochemicals to interfere with bacterial quorum sensing (QS) signaling pathways and underlying phenotypes is provided. The use of phytochemicals as chelating agents and efflux pump inhibitors is also reviewed.

Keywords: antibiofilm strategies; antibiotic adjuvants; efflux pump inhibition; metal chelators; multidrug resistance; plant compounds; quorum sensing inhibition.

Figure 1

Mechanisms involved in bacterial resistance to antibiotics.

Figure 2

Main mechanisms of biofilm resistance to antibiotics.

Figure 3

Main antibiofilm strategies. The suggested approaches can be divided in two major lines of action: some are meant to prevent biofilm formation and others to eradicate established biofilms, and they can comprise the application of physical, chemical and biological methods. Some of them such as QSI, chelating agents and the use of natural compounds from plants (phytochemicals) can be applied for both biofilm inhibition and eradication. Although the second messenger c-di-GMP is mainly involved in the transition of the planktonic to sessile state, it can be also used as a target to disperse biofilms. The use of photodynamic therapy and nanoparticles as drug carriers is not specific for biofilm removal, as they can be useful to inhibit biofilm formation.

Figure 4

Examples of plant-based molecules able to inhibit QS-regulated processes.

Figure 4

Examples of plant-based molecules able to inhibit QS-regulated processes.

Figure 4

Examples of plant-based molecules able to inhibit QS-regulated processes.