Beyond Bacteria: Bacteriophage-Eukaryotic Host Interactions Reveal Emerging Paradigms of Health and Disease

Abstract

For decades, a wealth of information has been acquired to define how host associated microbial communities contribute to health and disease. Within the human microbiota this has largely focused on bacteria, yet there is a myriad of viruses that occupy various tissue sites, the most abundant being bacteriophages that infect bacteria. Animal hosts are colonized with niche specific microbial communities where bacteria are continuously co-evolving with phages. Bacterial growth, metabolic activity, pathogenicity, antibiotic resistance, interspecies competition and evolution can all be influenced by phage infection and the beneficial nature of such interactions suggests that to an extent phages are tolerated by their hosts. With the understanding that phage-specific host-microbe interactions likely contribute to bacterial interactions with their mammalian hosts, phages and their communities may also impact aspects of mammalian health and disease that have gone unrecognized. Here, we review recent progress in understanding how bacteria acquire and tolerate phage in both pure culture and within complex communities. We apply these findings to discuss how intra-body phages interact with bacteria to influence their eukaryotic hosts through potential contributions to microbial homeostasis, mucosal immunity, immune tolerance and autoimmunity.

Keywords: bacteriophage; host–microbe interactions; microbiome; microbiota; phage immunity; phage–bacteria interactions; virome.

FIGURE 1

Bacteriophages contribute to the genetic and physiological traits of their hosts thereby influencing host–microbe interactions. (A) Schematic representation of a healthy mammalian microbiota consisting of heterogeneous phage and bacterial populations. The prolonged and ubiquitous presence of phages in mammalian microbiotas are hypothesized to have considerable effects on health and disease. Phage-driven impacts on mammalian hosts include (B) immune tolerance, (C) mucosal immunity, and (D) homeostatic eubiosis. Altered phage diversity and richness have been suggested to drive (E) bacterial dysbiosis, potentially leading to (E-1) autoimmune progression in type I diabetes and (E-2) inflammation during inflammatory bowel disease. On the other hand, phage infection endows bacteria with multiple features that alter bacterial interactions with their mammalian hosts. (F) Lysogenic conversion via the acquisition of prophages can increase bacterial host fitness. Prophage provided traits include (F-1) superinfection immunity, (F-2) elimination of bacterial competitors, (F-3) horizontal gene transfer, (F-4) enhanced antibiotic resistance, (F-5) virulence, and (F-6) altered gene expression.