We Are One: Multispecies Metabolism of a Biofilm Consortium and Their Treatment Strategies

Abstract

The ecological and medical significance of bacterial biofilms have been well recognized. Biofilms are harder to control than their planktonic free-living counterparts and quite recently, the focus of the study has shifted to the multispecies consortia, which represent the vast majority of real-case infection scenarios. Studies have begun to explore the complex interspecies interactions within these biofilms. However, only little attention is currently given to the role of cellular metabolites in the cell-to-cell communication. The concentration gradients of metabolic substrates and products affect the spatial growth of bacteria in multispecies biofilm. This, if looked into more deeply, can lead to identification of potential therapies targeting the specific metabolites and hence the coordinated protection in the bacterial community. Herein, we review the interspecies communications, including their metabolic cross-talking, in multispecies biofilm, to signify the importance of such interactions on the initial formation and subsequent growth of these biofilms. Multispecies biofilms with their species heterogeneity are more resilient to antimicrobial agents than their single species biofilm counterparts and this characteristic is of particular interest when dealing with pathogenic bacteria. In this Review, we also discuss the treatment options available, to include current and emerging avenues to combat pathogenic multispecies biofilms in the clinical, environmental, as well as industrial settings.

Keywords: biofilms; interactions; metabolism; multispecies; treatment.

FIGURE 1

Schematic representation of the mechanisms of interspecies interactions in multispecies biofilms and innovative biofilm-therapeutic strategies. (1) Horizontal gene transfer via plasmid conjugation, where plasmid (black circles) is transferred from one species (green cells) to another (blue cells). (2) Quorum sensing through intraspecific (black stars) and interspecific (wifi signals) communication by diffusible molecules. (3) Metabolic cooperation where the by-product of one species (green cells) serve as nutrient (black hexagons) for another species (red cells). (4) Physical interactions, where specific cell-to-cell interactions occurs between cells of different species through specific cell surface receptors. Available treatment options to combat biofilms are depicted in illustrations around the biofilm, with yellow arrows pointing to their target in the biofilm. NPs: Nanoparticles, eDNA: extracellular DNA. Created using Biorender.