Opportunities and challenges in managing antibiotic resistance in bacteria using plant secondary metabolites

Abstract

Development of antibiotic resistance (ABR) in bacteria and its multidimensional spread is an emerging global threat that needs immediate attention. Extensive antibiotics (AB) usage results in development of ABR in bacteria by target modification, production of AB degrading enzymes, porin modifications, efflux pumps overexpression, etc. To counter this, apart from strict regulation of AB use and behavioural changes, research and development (R&D) of newer antimicrobials are in place. One such emerging approach to combat ABR is the use of structurally and functionally diverse plant secondary metabolites (PSMs) in combination with the conventional AB. Either the PSMs are themselves antimicrobial or they potentiate the activity of the AB through a range of mechanisms. However, their use is lagging due to poor knowledge of mode of action, structure-activity relationships, pharmacokinetics, etc. This review paper discussed the opportunities and challenges in managing ABR using PSMs. Mechanisms of ABR development in bacteria and current strategies to counter them were studied and the areas where PSMs can play an important role were highlighted. The use of PSMs, both as an anti-resistance and anti-virulence agent in combination therapy to counter multi-drug resistance along with their mechanisms of action, has been discussed in detail. The difficulties in the commercialisation of PSMs and strategies to overcome them along with future priority areas of research have also been given. Following the given R&D path will definitely help in better understanding and utilising the full potential of PSMs in solving the problem of antimicrobial resistance (AMR).

Keywords: Antibiotic resistance; Anti–virulence; Bioavailability; Combinatorial therapy; Plant secondary metabolites; Potentiating activity.