Bacterial viruses are among the most numerous biological entities within the human body. These viruses are found within regions of the body that have conventionally been considered sterile, including the blood, lymph, and organs. However, the primary mechanism that bacterial viruses use to bypass epithelial cell layers and access the body remains unknown. Here, we used in vitro studies to demonstrate the rapid and directional transcytosis of diverse bacteriophages across confluent cell layers originating from the gut, lung, liver, kidney, and brain. Bacteriophage transcytosis across cell layers had a significant preferential directionality for apical-to-basolateral transport, with approximately 0.1% of total bacteriophages applied being transcytosed over a 2-h period. Bacteriophages were capable of crossing the epithelial cell layer within 10 min with transport not significantly affected by the presence of bacterial endotoxins. Microscopy and cellular assays revealed that bacteriophages accessed both the vesicular and cytosolic compartments of the eukaryotic cell, with phage transcytosis suggested to traffic through the Golgi apparatus via the endomembrane system. Extrapolating from these results, we estimated that 31 billion bacteriophage particles are transcytosed across the epithelial cell layers of the gut into the average human body each day. The transcytosis of bacteriophages is a natural and ubiquitous process that provides a mechanistic explanation for the occurrence of phages within the body. IMPORTANCE Bacteriophages (phages) are viruses that infect bacteria. They cannot infect eukaryotic cells but can penetrate epithelial cell layers and spread throughout sterile regions of our bodies, including the blood, lymph, organs, and even the brain. Yet how phages cross these eukaryotic cell layers and gain access to the body remains unknown. In this work, epithelial cells were observed to take up and transport phages across the cell, releasing active phages on the opposite cell surface. Based on these results, we posit that the human body is continually absorbing phages from the gut and transporting them throughout the cell structure and subsequently the body. These results reveal that phages interact directly with the cells and organs of our bodies, likely contributing to human health and immunity.

We present a particle separation mechanism which induces the motion of particles of different sizes in opposite directions. The mechanism is based on the combined action of a driving force and an entropic rectification of the Brownian fluctuations caused by the asymmetric form of the channel along which particles proceed. The entropic splitting effect shown could be controlled upon variation of the geometrical parameters of the channel and could be implemented in narrow channels and microfluidic devices.

Summary: Lysogens are common at high bacterial densities, an observation that contrasts with the prevailing view of lysogeny as a low‐density refugium strategy. Here, we review the mechanisms regulating lysogeny in complex communities and show that the additive effects of coinfections, diversity and host energic status yield a bimodal distribution of lysogeny as a function of microbial densities. At high cell densities (above 10 ⁶ cells ml ⁻¹ or g ⁻¹ ) and low diversity, coinfections by two or more phages are frequent and excess energy availability stimulates inefficient metabolism. Both mechanisms favour phage integration and characterize the Piggyback‐the‐Winner dynamic. At low densities (below 10 ⁵ cells ml ⁻¹ or g ⁻¹ ), starvation represses lytic genes and extends the time window for lysogenic commitment, resulting in a higher frequency of coinfections that cause integration. This pattern follows the predictions of the refugium hypothesis. At intermediary densities (between 10 ⁵ and 10 ⁶ cells ml ⁻¹ or g ⁻¹ ), encounter rates and efficient energy metabolism favour lysis. This may involve Kill‐the‐Winner lytic dynamics and induction. Based on these three regimes, we propose a framework wherein phage integration occurs more frequently at both ends of the host density gradient, with distinct underlying molecular mechanisms (coinfections and host metabolism) dominating at each extreme.

Viruses have evolved protein containers with a wide spectrum of icosahedral architectures to protect their genetic material. The geometric constraints defining these container designs, and their implications for viral evolution, are open problems in virology. The principle of quasi-equivalence is currently used to predict virus architecture, but improved imaging techniques have revealed increasing numbers of viral outliers. We show that this theory is a special case of an overarching design principle for icosahedral, as well as octahedral, architectures that can be formulated in terms of the Archimedean lattices and their duals. These surface structures encompass different blueprints for capsids with the same number of structural proteins, as well as for capsid architectures formed from a combination of minor and major capsid proteins, and are recurrent within viral lineages. They also apply to other icosahedral structures in nature, and offer alternative designs for man-made materials and nanocontainers in bionanotechnology.