Lysogeny in nature: mechanisms, impact and ecology of temperate phages

Abstract

Viruses that infect bacteria (phages) can influence bacterial community dynamics, bacterial genome evolution and ecosystem biogeochemistry. These influences differ depending on whether phages establish lytic, chronic or lysogenic infections. Although the first two produce virion progeny, with lytic infections resulting in cell destruction, phages undergoing lysogenic infections replicate with cells without producing virions. The impacts of lysogeny are numerous and well-studied at the cellular level, but ecosystem-level consequences remain underexplored compared to those of lytic infections. Here, we review lysogeny from molecular mechanisms to ecological patterns to emerging approaches of investigation. Our goal is to highlight both its diversity and importance in complex communities. Altogether, using a combined viral ecology toolkit that is applied across broad model systems and environments will help us understand more of the diverse lifestyles and ecological impacts of lysogens in nature.

Figure 1

Modes of temperate phage infection, from cell to community. (a) A temperate phage can infect a cell through either virion-productive or lysogenic cycles, where it either hijacks its host’s metabolism to produce new virion progeny or instead replicates its genome alongside the host without producing new virions, respectively. The production of virion particles can occur either following phage adsorption (productive cycle) or instead following a switch from a lysogenic cycle to a productive cycle (lytic or instead chronic infection cycles depending on the temperate phage). Although these are generalized dynamics of infection, details can vary with specific phage-host types, ranging from efficient to inefficient infections, where the dynamics and outcome of the infection may vary. (b) Summary of phage infection strategies by stage. Persistence describes the prophage stage during the lysogenic cycle, replication describes the phage-genome state during productive cycles and release refers not just to the means by which progeny phage virions transition from the intracellular to extracellular state but also the impact of productive cycles on the phage-infected bacterium (i.e., lytic but not chronic results in host-bacterium physiological death). (c) Implications of modes of temperate phage infection on bacterial communities. Lysogenic conversion constitutes the phenotypic effects of prophage carriage to its host cell. The lysogenic to lytic switch changes community structure by creating a mixed cell community where some lysogens are removed via lysis and the released virions can infect surrounding cells. Polylysogeny occurs when a bacterium possesses multiple prophages.

Figure 2

Ecology of lysogeny. The establishment and maintenance of lysogeny in the cell depends on the genotype of phage and host, the physiological status of the cell, and phage concentration. In nature, temperate phage-host cell interactions are influenced by multiple factors, ranging from biological (e.g., cell development and community dynamics) to environmental (e.g., factors that cause stress and environmental fluctuations). Altogether, the interplay of all of these factors may help to explain the incidence of lysogeny across different systems, including aquatic, terrestrial and microbiome-associated (e.g., as associated with humans, animals and so on).

Figure 3

Approaches and methods pipeline for characterizing lysogeny. Multiple approaches to investigating lysogeny can be applied to a bacterial community either prior to induction, following induction or to isolate samples. Community samples may be divided into bacterial and viral fractions, where the DNA can be sequenced (metagenomics) and prophages analyzed bioinformatically. In addition, sequencing RNA (metatranscriptomics) and protein (metaproteomics) may provide information on abundance and activity. Treatment of samples with inducing agents (e.g., mitomycin C, UV radiation) can measure the proportion of lysogens that are sensitive to such treatment by detecting the switch from lysogenic to productive (generally lytic) cycles. Information of phage-cell interactions can be obtained by culturing and isolating lysogens from environmental samples, which can then be treated for induction and/or analyzed in detail genetically, molecularly and structurally (microscopy). Techniques such as ‘omics (transcriptomics, proteomics, metabolomics) allow characterization of molecular changes during infection. When paired with single-cell resolution, infection dynamics can be followed to determine the prophage type (e.g., integrated versus extrachromosomal) and the fraction of infected and lysed cells. A combination of these approaches can inform the distribution, abundance and types of temperate phages, lysogens, and uninfected hosts, as well as increase our mechanistic understanding of the establishment, maintenance and dynamics of temperate phage infections.