Polymicrobial Biofilms: Interkingdom Interactions, Resistance and Therapeutic Strategies

Polymicrobial biofilms are a conglomeration of diverse microbial consortia encased in a self-produced exopolysaccharide layer that forms on any biotic or abiotic surface. They are more resilient and persistent due to their enhanced drug resistance compared to monospecies biofilms, making it more difficult to eliminate using standard antimicrobial therapies. The present review discusses various inter- and intra-kingdom interactions taking place in polymicrobial biofilms and accounts for the various underlying drug resistance mechanisms in this complex and heterogeneous niche. In addition, this review provides insights into developing new diagnostic approaches by exploiting metabolites and byproducts produced by drug-resistant pathogens and other microorganisms in polymicrobial biofilms. As drug resistance is an ever-evolving mechanism in polymicrobial biofilms, synergistic combinations of natural products and antibiotics alone are not a panacea for eradicating these drug-resistant polymicrobial biofilms. Therefore, this review summarises both chemical and physical measures undertaken to combat these drug-resistant biofilms and stresses the need to employ 'omics' approaches, gene editing technologies and the integration of artificial intelligence/machine learning tools as future perspectives to eradicate these complex biofilms.