Big Impact of the Tiny: Bacteriophage–Bacteria Interactions in Biofilms

Biofilm maturation and composition is crucial for phage susceptibility of bacteria. The therapeutic use of phages and their enzymes is a promising supplement to conventional treatment strategies of bacterial infections. Both prophages and free phages can promote biofilm formation, which may increase protection and diversification of both phages and bacterial hosts. Future investigations of phage–host dynamics in multispecies consortia are required to elucidate how interspecies interactions and community-intrinsic properties affect phage infections. Bacteriophages (phages) have been shaping bacterial ecology and evolution for millions of years, for example, by selecting for defence strategies. Evidence supports that bacterial biofilm formation is one such strategy and that biofilm-mediated protection against phage infection depends on maturation and composition of the extracellular matrix. Interestingly, studies have revealed that phages can induce and strengthen biofilms. Here we review interactions between bacteria and phages in biofilms, discuss the underlying mechanisms, the potential of phage therapy for biofilm control, and emphasize the importance of considering biofilms in future phage research. This is especially relevant as biofilms are associated with increased tolerance towards antibiotics and are implicated in the majority of chronic infections. Bacteriophages (phages) have been shaping bacterial ecology and evolution for millions of years, for example, by selecting for defence strategies. Evidence supports that bacterial biofilm formation is one such strategy and that biofilm-mediated protection against phage infection depends on maturation and composition of the extracellular matrix. Interestingly, studies have revealed that phages can induce and strengthen biofilms. Here we review interactions between bacteria and phages in biofilms, discuss the underlying mechanisms, the potential of phage therapy for biofilm control, and emphasize the importance of considering biofilms in future phage research. This is especially relevant as biofilms are associated with increased tolerance towards antibiotics and are implicated in the majority of chronic infections. major extracellular proteinaceous aggregates with high stability and physical robustness. agents able to prevent microbial growth or kill microbial organisms. a mechanism facilitating horizontal gene transfer. Progeny phage particles released by prophage induction in a fraction of the population can infect other susceptible bacteria and form transducing particles packed with bacterial DNA, not associated with phage genome, and hence introduce novel DNA to the remaining population of lysogens. the number of phage virions released per infected cell. properties emerging in communities which are unpredictable by studying the individual parts in isolation. self-transmissible plasmids encoding the components required for conjugation. a promiscuous active transporter of various compounds including toxic substrates, for example antibiotics. transfer of genetic material between organisms, for example, by uptake of free DNA (transformation), mediated by phages (transduction) or mediated by mobilizable plasmids (conjugation). the probability of temperate phages to either produce progeny phage particles or establish lysogeny, depending on cues, for example, the level of arbitrium peptides. a well-mixed system in which collisions occur at random. cell aggregates confined within a matrix of polymeric substances. a phage without the genes required for prophage establishment, which consistently lyses a susceptible host upon infection. stochastically arising metabolically inactive variants which enable reoccurrence of chronic infections due to high antibiotic tolerance. the use of phages for therapeutic applications, for example, to treat bacterial infections in humans. phage genome integrated into a bacterial host chromosome. a system that enables bacteria to monitor population density and regulate gene expression accordingly based on the production and detection of specific signal molecules, termed autoinducers. when the outcome is higher than the additive sum of individual effects. phages with the ability to integrate into a host chromosome, establish a prophage, and excise, producing progeny phages, at a later timepoint.