Unconstrained coevolution of bacterial size and the latent period of plastic phage

Viruses play critical roles in the dynamics of microbial communities. Lytic viruses, for example, kill significant proportions of autotrophic and heterotrophic microbes. The dynamic interplay between viruses and microbes results from an overlap of physiological, ecological, and evolutionary responses: environmental changes trigger host physiological changes, affecting the ecological interactions of host and virus and, ultimately, the evolutionary pressures influencing the two populations. Recent theoretical work studied how the dependence of viral traits on host physiology (viral plasticity) affects the evolutionarily stable host cell size and viral infection time emerging from coevolution. Here, we broaden the scope of the framework to consider any coevolutionary outcome, including potential evolutionary collapses of the system. We used the case study of Escherichia coli and T-like viruses under chemostat conditions, but the framework can be adapted to any microbe-virus system. Oligotrophic conditions led to smaller, lower-quality but more abundant hosts, and infections that were longer but produced a reduced viral offspring. Conversely, eutrophic conditions resulted in fewer but larger higher-quality hosts, and shorter but more productive infections. The virus influenced host evolution decreasing host radius more noticeably for low than for high dilution rates, and for high than for low nutrient input concentration. For low dilution rates, the emergent infection time minimized host need/use, but higher dilution led to an opportunistic strategy that shortened the duration of infections. System collapses driven by evolution resulted from host failure to adapt quickly enough to the evolving virus. Our results contribute to understanding the eco-evolutionary dynamics of microbes and virus, and to improving the predictability of current models for host-virus interactions. The large quantitative and qualitative differences observed with respect to a classic description (in which viral traits are assumed to be constant) highlights the importance of including viral plasticity in theories describing short- and long-term host-virus dynamics.

Analysis of Infection Time Courses Shows CII Levels Determine the Frequency of Lysogeny in Phage 186

Engineered phage with properties optimised for the treatment of bacterial infections hold great promise, but require careful characterisation by a number of approaches. Phage–bacteria infection time courses, where populations of bacteriophage and bacteria are mixed and followed over many infection cycles, can be used to deduce properties of phage infection at the individual cell level. Here, we apply this approach to analysis of infection of Escherichia coli by the temperate bacteriophage 186 and explore which properties of the infection process can be reliably inferred. By applying established modelling methods to such data, we extract the frequency at which phage 186 chooses the lysogenic pathway after infection, and show that lysogenisation increases in a graded manner with increased expression of the lysogenic establishment factor CII. The data also suggest that, like phage λ, the rate of lysogeny of phage 186 increases with multiple infections.

Adjusting for time of infection or positive test when estimating the risk of a post-infection outcome in an epidemic

When comparing the risk of a post-infection binary outcome, e.g. hospitalisation, for two variants of an infectious pathogen, it is important to adjust for calendar time of infection to avoid the confounding that would occur if the relative incidence of the two variants and the variant-specific risks of the outcome both change over time. Infection time is typically unknown and time of positive test used instead. Likewise, time of positive test may be used instead of infection time when assessing how the risk of the binary outcome changes over calendar time. Here we show that if mean time from infection to positive test is correlated with the outcome, the risk conditional on positive test time depends on whether incidence of infection is increasing or decreasing over calendar time. This complicates interpretation of risk ratios adjusted for positive test time. We also propose a simple sensitivity analysis that indicates how these risk ratios may differ from the risk ratios adjusted for infection time.

Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals

With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.

RNA-Seq Transcriptome Analysis of Peripheral Blood From Cattle Infected With Mycobacterium bovis Across an Experimental Time Course

Bovine tuberculosis, caused by infection with members of the Mycobacterium tuberculosis complex, particularly Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including RNA sequencing, has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analysed the transcriptome of bovine whole peripheral blood samples collected at −1 week pre-infection and +1, +2, +6, +10, and +12 weeks post-infection time points. Differentially expressed genes were catalogued and evaluated at each post-infection time point relative to the −1 week pre-infection time point and used for the identification of putative candidate host transcriptional biomarkers for M. bovis infection. Differentially expressed gene sets were also used for examination of cellular pathways associated with the host response to M. bovis infection, construction of de novo gene interaction networks enriched for host differentially expressed genes, and time-series analyses to identify functionally important groups of genes displaying similar patterns of expression across the infection time course. A notable outcome of these analyses was identification of a 19-gene transcriptional biosignature of infection consisting of genes increased in expression across the time course from +1 week to +12 weeks post-infection.

Evolutionarily Stable Coevolution Between a Plastic Lytic Virus and Its Microbial Host

Hosts influence and are influenced by viral replication. Cell size, for example, is a fundamental trait for microbial hosts that can not only alter the probability of viral adsorption, but also constrain the host physiological processes that the virus relies on to replicate. This intrinsic connection can affect the fitness of both host and virus, and therefore their mutual evolution. Here, we study the coevolution of bacterial hosts and their viruses by considering the dependence of viral performance on the host physiological state (viral plasticity). To this end, we modified a standard host-lytic phage model to include viral plasticity, and compared the coevolutionary strategies emerging under different scenarios, including cases in which only the virus or the host evolve. For all cases, we also obtained the evolutionary prediction of the traditional version of the model, which assumes a non-plastic virus. Our results reveal that the presence of the virus leads to an increase in host size and growth rate in the long term, which benefits both interacting populations. Our results also show that viral plasticity and evolution influence the classic host quality-quantity trade-off. Poor nutrient environments lead to abundant low-quality hosts, which tends to increase viral infection time. Conversely, richer nutrient environments lead to fewer but high-quality hosts, which decrease viral infection time. Our results can contribute to advancing our understanding of the microbial response to changing environments. For instance, both cell size and viral-induced mortality are essential factors that determine the structure and dynamics of the marine microbial community, and therefore our study can improve predictions of how marine ecosystems respond to environmental change. Our study can also help devise more reliable strategies to use phage to, for example, fight bacterial infections.

Effects of Physicochemical Factors on Loss of Infectivity of Opisthorchis viverrini Cercariae

This study aims to develop an alternative field-based approach to interrupt the life cycle of O. viverrini. The effects of temperature, salinity, acidity, ultraviolet A, B, C radiation, and combinations of these physicochemical factors on the loss of infectivity of Opisthorchis viverrini cercariae were analyzed to determine values required for 50 and 95 % lethal concentrations (LC50 and LC95) and period of loss infection success (LI50 and LI95). Newly shed cercariae of O. viverrini were used. LC50 and LC95 values for temperature, salinity, and acidity on cercariae were 33.19 and 37.70 ºC, 7.29 and 8.40 ppt, 4.62 and 4.80 M H2CO3, respectively. The values of LI50 and LI95 on cercariae by exposure to UVA, UVB, and UVC were 19.54 and 20.11 h, 5.03 and 5.12 h, 3.37 and 6.02 min, respectively. Combinations of these factors in the presence of UVC proved damaging to cercariae most rapidly. The shortest loss infection time of LI50 and LI95 were 1.09 and 2.83 min. Cercariae were deemed to have lost the ability to infect cyprinid fish when they had shed their tails, even though they were still capable of some movement. In nature, temperature, salinity, acidity, ultraviolet radiation, and combinations of these factors, affect the ability of O. viverrini cercariae to infect cyprinid fish.

Previous SARS-CoV-2 infection increases B.1.1.7 cross-neutralization by vaccinated individuals.

To assess the potential impact of predominant circulating SARS-CoV-2 variants on neutralizing activity of infected and/or vaccinated individuals, we analyzed neutralization of pseudoviruses expressing the spike of the original Wuhan strain, the D614G and B.1.1.7 variants. Our data show that parameters of natural infection (time from infection and infecting variant) determined cross-neutralization. Importantly, upon vaccination, previously infected individuals developed equivalent B.1.1.7 and Wuhan neutralizing responses. In contrast, uninfected vaccinees showed reduced neutralization against B.1.1.7.