Piggyback-the-Winner in host-associated microbial communities

Abstract

Phages can exploit their bacterial hosts by lytic infection, when many viral particles are released at cell lysis, or by lysogeny, when phages integrate into the host's genome. We recently proposed a new dynamic model of bacteria-phage interactions in which lysogeny predominates at high microbial abundance and growth rates. This model, named Piggyback-the-Winner (PtW), contrasts to current accepted models on the frequency of lysis and lysogeny and predicts that phages integrate into their hosts' genomes as prophages when microbial abundances and growth rates are high. According to PtW, switching to the temperate life cycle reduces phage predation control on bacterial abundance and confers superinfection exclusion, preventing that a closely-related phage infects the same bacterial cell. Here we examine how PtW is important for metazoans. Specifically, we postulate that PtW and the recently described bacteriophage adherence to mucus (BAM) model are strongly interrelated and have an important role in the development of the microbiome. In BAM, phage produced by the microbiome attach to mucins and protect underlying epithelial cells from invading bacteria. Spatial structuring of the mucus creates a gradient of phage replication strategies consistent with PtW. We predict that lysogeny is favored at the top mucosal layer and lytic predation predominates in the bacteria-sparse intermediary layers. The lysogeny confers competitive advantage to commensals against niche invasion and the lytic infection eliminates potential pathogens from deeper mucus layers.

Figure 1

Spatially structured lytic to lysogenic switches in microbial communities associated to metazoan mucosal surfaces. The bottom nucleated cell layer represents the metazoan host epithelium. A mucin concentration gradient is formed from the epithelium to the top. Commensal bacteria abundance (blue flagellated cells) is higher at the top layer where mucin concentration is low, whereas phage abundance is higher at intermediate layers as a result to direct adherence to mucus. High bacterial abundance and growth at the top layers favours lysogeny, while lysis is favoured at the intermediate layer. An invading pathogen (red flagellated cell) encounter two steps of phage-mediated immunity: (1) competition with commensal lysogens displaying high fitness resulting from the integrated phage genome; (2) lytic infection at intermediate layers. An invasive lysogen containing a prophage that confers high fitness gain could outcompete commensals and scape lytic infection by maintaining high growth rates, leading to the establishment of infection.