Antoni Luque

Lytic to temperate switching of viral communities

Microbial viruses can control host abundances via density-dependent lytic predator–prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus ‘more microbes, fewer viruses’.

The chromatin fiber: Multiscale problems and approaches

The structure of chromatin, affected by many factors from DNA linker lengths to posttranslational modifications, is crucial to the regulation of eukaryotic cells. Combined experimental and computational methods have led to new insights into its structural and dynamical features, from interactions due to the flexible core histone tails or linker histones to the physical mechanism driving the formation of chromosomal domains. Here we present a perspective of recent advances in chromatin modeling techniques at the atomic, mesoscopic, and chromosomal scales with a view toward developing multiscale computational strategies to integrate such findings. Innovative modeling methods that connect molecular to chromosomal scales are crucial for interpreting experiments and eventually deciphering the complex dynamic organization and function of chromatin in the cell.

Dynamic condensation of linker histone C-terminal domain regulates chromatin structure

The basic and intrinsically disordered C-terminal domain (CTD) of the linker histone (LH) is essential for chromatin compaction. However, its conformation upon nucleosome binding and its impact on chromatin organization remain unknown. Our mesoscale chromatin model with a flexible LH CTD captures a dynamic, salt-dependent condensation mechanism driven by charge neutralization between the LH and linker DNA. Namely, at low salt concentration, CTD condenses, but LH only interacts with the nucleosome and one linker DNA, resulting in a semi-open nucleosome configuration; at higher salt, LH interacts with the nucleosome and two linker DNAs, promoting stem formation and chromatin compaction. CTD charge reduction unfolds the domain and decondenses chromatin, a mechanism in consonance with reduced counterion screening in vitro and phosphorylated LH in vivo. Divalent ions counteract this decondensation effect by maintaining nucleosome stems and expelling the CTDs to the fiber exterior. Additionally, we explain that the CTD folding depends on the chromatin fiber size, and we show that the asymmetric structure of the LH globular head is responsible for the uneven interaction observed between the LH and the linker DNAs. All these mechanisms may impact epigenetic regulation and higher levels of chromatin folding.

Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers

ABSTRACT 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. 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.

Theoretical Studies on Assembly, Physical Stability and Dynamics of Viruses

All matter has to obey the general laws of physics and living matter is not an exception. Viruses have not only learnt how to cope with them, but have managed to use them for their own survival. In this chapter we will review some of the exciting physics behind viruses and discuss simple physical models that can shed some light on different aspects of the viral life cycle and viral properties. In particular, we will focus on how the structure and shape of the capsid, its assembly and stability, and the entry and exit of viral particles and their genomes can be understood using fundamental physics theories.

Variability and host density independence in inductions-based estimates of environmental lysogeny

Temperate bacterial viruses (phages) may enter a symbiosis with their host cell, forming a unit called a lysogen. Infection and viral replication are disassociated in lysogens until an induction event such as DNA damage occurs, triggering viral-mediated lysis. The lysogen–lytic viral reproduction switch is central to viral ecology, with diverse ecosystem impacts. It has been argued that lysogeny is favoured in phages at low host densities. This paradigm is based on the fraction of chemically inducible cells (FCIC) lysogeny proxy determined using DNA-damaging mitomycin C inductions. Contrary to the established paradigm, a survey of 39 inductions publications found FCIC to be highly variable and pervasively insensitive to bacterial host density at global, within-environment and within-study levels. Attempts to determine the source(s) of variability highlighted the inherent complications in using the FCIC proxy in mixed communities, including dissociation between rates of lysogeny and FCIC values. Ultimately, FCIC studies do not provide robust measures of lysogeny or consistent evidence of either positive or negative host density dependence to the lytic–lysogenic switch. Other metrics are therefore needed to understand the drivers of the lytic–lysogenic decision in viral communities and to test models of the host density-dependent viral lytic–lysogenic switch.

Corrigendum: Lytic to temperate switching of viral communities.

This corrects the article DOI: 10.1038/nature17193

Relevance of coral geometry in the outcomes of the coral-algal benthic war

Corals have built reefs on the benthos for millennia, becoming an essential element in marine ecosystems. Climate change and human impact, however, are favoring the invasion of non-calcifying benthic algae and reducing coral coverage. Corals rely on energy derived from photosynthesis and heterotrophic feeding, which depends on their surface area, to defend their outer perimeter. But the relation between geometric properties of corals and the outcome of competitive coral-algal interactions is not well known. To address this, 50 coral colonies interacting with algae were sampled in the Caribbean island of Curaçao. 3D and 2D digital models of corals were reconstructed to measure their surface area, perimeter, and polyp sizes. A box counting algorithm was applied to calculate their fractal dimension. The perimeter and surface dimensions were statistically non-fractal, but differences in the mean surface fractal dimension captured relevant features in the structure of corals. The mean fractal dimension and surface area were negatively correlated with the percentage of losing perimeter and positively correlated with the percentage of winning perimeter. The combination of coral perimeter, mean surface fractal dimension, and coral species explained 19% of the variability of losing regions, while the surface area, perimeter, and perimeter-to-surface area ratio explained 27% of the variability of winning regions. Corals with surface fractal dimensions smaller than two and small perimeters displayed the highest percentage of losing perimeter, while corals with large surface areas and low perimeter-to-surface ratios displayed the largest percentage of winning perimeter. This study confirms the importance of fractal surface dimension, surface area, and perimeter of corals in coral-algal interactions. In combination with non-geometrical measurements such as microbial composition, this approach could facilitate environmental conservation and restoration efforts on coral reefs.

Correction for Nguyen et al., “Bacteriophage Transcytosis Provides a Mechanism To Cross Epithelial Cell Layers”

Volume 8, no. 6, e01874-17, 2017, [https://doi.org/10.1128/mBio.01874-17][1]. The following funding information and acknowledgments should be added: This work, including the efforts of Benjamin S. Padman and Michael Lazarou, was funded by an Australian Research Council (ARC) Future Fellowship (