Genomic and ecological attributes of marine bacteriophages encoding bacterial virulence genes

Benler

Lee

et al. 2020

Preprint

Self Cite

Tailed phages are the most abundant and diverse group of viruses on the planet. Yet, the smallest tailed phages display relatively complex capsids and large genomes compared to other viruses. The lack of tailed phages forming the common icosahedral capsid architectures T = 1 and T = 3 is puzzling. Here, we extracted geometrical features from high-resolution tailed phage capsid reconstructions and built a statistical model based on physical principles to predict the capsid diameter and genome length of the missing small tailed phage capsids. We applied the model to 3,348 isolated tailed phage genomes and 1,496 gut metagenome-assembled tailed phage genomes. Four isolated tailed phages were predicted to form T = 3 icosahedral capsids, and twenty-one metagenome-assembled tailed phages were predicted to form T < 3 capsids. The smallest capsid predicted was a T = 4/3 ≈ 1.33 architecture. No tailed phages were predicted to form the smallest icosahedral architecture, T = 1. We discuss the feasibility of the missing T = 1 tailed phage capsids and the implications of isolating and characterizing small tailed phages for viral evolution and phage therapy.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Missing Tailed Phages: Prediction of Small Capsid Candidates

Benler

Lee

et al. 2020

Preprint

Self Cite

“…It resulted into a higher contribution from the dominant ranks to lysogeny (Figure 4d). While the positive relationship between phage and host abundance has been shown for some dominant species in marine and gut samples (Deng et al , 2013; Zhao et al , 2013; Džunková et al , 2019), the prediction of phage hosts from genomic data is a current challenge, and the host of most phages identified through metagenomics remain unknown (Edwards et al , 2016; Gregory et al , 2019; Silveira et al , 2020). The reconstruction of accurate phage-bacterial infection networks will in the future improve the models’ predictive power (Labonté et al , 2015; Marbouty et al , 2017).…”

Section: Discussionmentioning

confidence: 99%

Quantification of lysogeny caused by phage coinfections in microbial communities from biophysical principles

Silveira

2020

Preprint

Self Cite

19Temperate phages can integrate in their bacterial host genome to form a lysogen, often 20 modifying the phenotype of the host. Lysogens are dominant in the microbial-dense 21 environment of the mammalian-gut. This observation contrasts with the long-standing 22 hypothesis of lysogeny being favored in microbial communities with low densities. Here we 23 hypothesized that phage coinfections-the most studied molecular mechanism of lysogeny 24 in lambda phage-increases at high microbial abundances. To test this hypothesis, we 25 developed a biophysical model of coinfection and stochastically sampled ranges of phage 26 and bacterial concentrations, adsorption rates, lysogenic commitment times, and 27 community diversity from marine and gut microbiomes. Based on lambda experiments, a 28 Poisson process assessed the probability of lysogeny via coinfection in these ecosystems. In 29 90% of the sampled marine ecosystems, lysogeny stayed below 10% of the bacterial 30 community. In contrast, 25% of the sampled gut communities stayed above 25% of 31 lysogeny, representing an estimated nine trillion lysogens formed via phage coinfection in 32 the human gut every day. The prevalence of lysogeny in the gut was a consequence of the 33 higher densities and faster adsorption rates. In marine communities, which were 34 characterized by lower densities and phage adsorption rates, lysogeny via coinfection was 35 still possible for communities with long lysogenic commitments times. Our study suggests 36 that physical mechanisms can favor coinfection and cause lysogeny at poor growth 37 conditions (long commitment times) and in rich environments (high densities and 38 adsorption rates).39 40 3 Importance 41 42Phage integration in bacterial genomes manipulate microbial dynamics from the oceans to 43 the human gut. This phage-bacteria interaction, called lysogeny, is well-studied in 44 laboratory models, but its environmental drivers remain unclear. Here we quantified the 45 frequency of lysogeny via phage coinfection-the most studied mechanism of lysogeny-by 46 developing a biophysical model that incorporated a meta-analysis of the properties of 47 marine and gut microbiomes. Lysogeny was found to be more frequent in high-productive 48 environments like the gut, due to higher phage and bacterial densities and faster phage 49 adsorption rates. At low cell densities, lysogeny via coinfection was possible for hosts with 50 long duplication times. Our research bridges the molecular understanding of lysogeny with 51

“…If these closely related phages cooperate during the lysogenic decision, their summed abundances would be much higher than the abundance of the highest rank in our model, 0.8% for marine communities. One challenge in building accurate phage-bacterial infection networks to test these comparisons is that the hosts of the majority of phages identified from metagenomic analyses are unknown (8,54,55). The reconstruction of accurate infection networks will, in the future, improve the model's predictive power on the contribution of coinfections to lysogeny (56,57).…”

Section: Marine Gutmentioning

confidence: 99%

“…Currently, the best proxies to estimate the frequency of lysogeny in microbial communities are the distributions of integrases, excisionases, lysis repressors, and sequences with high similarity with reference prophages (7,8). The abundance of these markers in metagenomic data indicates that microbially dense environments, such as the mammalian gut, are dominated by temperate phages and bacterial lysogens (9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

Quantification of Lysogeny Caused by Phage Coinfections in Microbial Communities from Biophysical Principles

Silveira

2020

mSystems

Self Cite

Temperate phages can associate with their bacterial host to form a lysogen, often modifying the phenotype of the host. Lysogens are dominant in the microbially dense environment of the mammalian gut. This observation contrasts with the long-standing hypothesis of lysogeny being favored at low microbial densities, such as in oligotrophic marine environments. Here, we hypothesized that phage coinfections—a well-understood molecular mechanism of lysogenization—increase at high microbial abundances. To test this hypothesis, we developed a biophysical model of coinfection for marine and gut microbiomes. The model stochastically sampled ranges of phage and bacterial concentrations, adsorption rates, lysogenic commitment times, and community diversity from each environment. In 90% of the sampled marine communities, less than 10% of the bacteria were predicted to be lysogenized via coinfection. In contrast, 25% of the sampled gut communities displayed more than 25% of lysogenization. The probability of lysogenization in the gut was a consequence of the higher densities and higher adsorption rates. These results suggest that, on average, coinfections can form two trillion lysogens in the human gut every day. In marine microbiomes, which were characterized by lower densities and phage adsorption rates, lysogeny via coinfection was still possible for communities with long lysogenic commitment times. Our study indicates that different physical factors causing coinfections can reconcile the traditional view of lysogeny at poor host growth (long commitment times) and the recent Piggyback-the-Winner framework proposing that lysogeny is favored in rich environments (high densities and adsorption rates). IMPORTANCE The association of temperate phages and bacterial hosts during lysogeny manipulates microbial dynamics from the oceans to the human gut. Lysogeny is well studied in laboratory models, but its environmental drivers remain unclear. Here, we quantified the probability of lysogenization caused by phage coinfections, a well-known trigger of lysogeny, in marine and gut microbial environments. Coinfections were quantified by developing a biophysical model that incorporated the traits of viral and bacterial communities. Lysogenization via coinfection was more frequent in highly productive environments like the gut, due to higher microbial densities and higher phage adsorption rates. At low cell densities, lysogenization occurred in bacteria with long duplication times. These results bridge the molecular understanding of lysogeny with the ecology of complex microbial communities.