Biofilm Structure Promotes Coexistence of Phage-Resistant and Phage-Susceptible Bacteria

Encounters among bacteria and their viral predators (bacteriophages) are among the most common ecological interactions on Earth. These encounters are likely to occur with regularity inside surface-bound communities that microbes most often occupy in natural environments. Such communities, termed biofilms, are spatially constrained: interactions become limited to near neighbors, diffusion of solutes and particulates can be reduced, and there is pronounced heterogeneity in nutrient access and physiological state. It is appreciated from prior theoretical work that phage-bacteria interactions are fundamentally different in spatially structured contexts, as opposed to well-mixed liquid culture. Spatially structured communities are predicted to promote the protection of susceptible host cells from phage exposure, and thus weaken selection for phage resistance. The details and generality of this prediction in realistic biofilm environments, however, are not known. Here, we explore phage-host interactions using experiments and simulations that are tuned to represent the essential elements of biofilm communities. Our simulations show that in biofilms, phage-resistant cells-as their relative abundance increases-can protect clusters of susceptible cells from phage exposure, promoting the coexistence of susceptible and phage-resistant bacteria under a large array of conditions. We characterize the population dynamics underlying this coexistence, and we show that coexistence is recapitulated in an experimental model of biofilm growth measured with confocal microscopy. Our results provide a clear view into the dynamics of phage resistance in biofilms with single-cell resolution of the underlying cell-virion interactions, linking the predictions of canonical theory to realistic models and in vitro experiments of biofilm growth. IMPORTANCE In the natural environment, bacteria most often live in communities bound to one another by secreted adhesives. These communities, or biofilms, play a central role in biogeochemical cycling, microbiome functioning, wastewater treatment, and disease. Wherever there are bacteria, there are also viruses that attack them, called phages. Interactions between bacteria and phages are likely to occur ubiquitously in biofilms. We show here, using simulations and experiments, that biofilms will in most conditions allow phage-susceptible bacteria to be protected from phage exposure, if they are growing alongside other cells that are phage resistant. This result has implications for the fundamental ecology of phage-bacteria interactions, as well as the development of phage-based antimicrobial therapeutics

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Biofilm Structure Promotes Coexistence of Phage-Resistant and Phage-Susceptible Bacteria.

Encounters among bacteria and their viral predators (bacteriophages) are among the most common ecological interactions on Earth. These encounters are likely to occur with regularity inside surface-bound communities that microbes most often occupy in natural environments. Such communities, termed biofilms, are spatially constrained: interactions become limited to near neighbors, diffusion of solutes and particulates can be reduced, and there is pronounced heterogeneity in nutrient access and physiological state. It is appreciated from prior theoretical work that phage-bacteria interactions are fundamentally different in spatially structured contexts, as opposed to well-mixed liquid culture. Spatially structured communities are predicted to promote the protection of susceptible host cells from phage exposure, and thus weaken selection for phage resistance. The details and generality of this prediction in realistic biofilm environments, however, are not known. Here, we explore phage-host interactions using experiments and simulations that are tuned to represent the essential elements of biofilm communities. Our simulations show that in biofilms, phage-resistant cells-as their relative abundance increases-can protect clusters of susceptible cells from phage exposure, promoting the coexistence of susceptible and phage-resistant bacteria under a large array of conditions. We characterize the population dynamics underlying this coexistence, and we show that coexistence is recapitulated in an experimental model of biofilm growth measured with confocal microscopy. Our results provide a clear view into the dynamics of phage resistance in biofilms with single-cell resolution of the underlying cell-virion interactions, linking the predictions of canonical theory to realistic models and in vitro experiments of biofilm growth.IMPORTANCE In the natural environment, bacteria most often live in communities bound to one another by secreted adhesives. These communities, or biofilms, play a central role in biogeochemical cycling, microbiome functioning, wastewater treatment, and disease. Wherever there are bacteria, there are also viruses that attack them, called phages. Interactions between bacteria and phages are likely to occur ubiquitously in biofilms. We show here, using simulations and experiments, that biofilms will in most conditions allow phage-susceptible bacteria to be protected from phage exposure, if they are growing alongside other cells that are phage resistant. This result has implications for the fundamental ecology of phage-bacteria interactions, as well as the development of phage-based antimicrobial therapeutics

Effect of a lifestyle intervention during pregnancy-findings from the Finnish gestational diabetes prevention trial (RADIEL)

Objective To assess the effect of lifestyle counseling on perinatal outcomes among women at high risk for gestational diabetes. Study design A total of 492 women with obesity and/or prior gestational diabetes were allocated to intervention (four sessions of lifestyle counseling, n = 249) or usual care (n = 243) before 20 weeks' gestation. Result Lifestyle indicators, gestational weight gain, or obstetric and perinatal outcomes did not differ between the two groups. An oral glucose tolerance test in the first half of pregnancy was pathological in 37.7% (n = 87/144) of intervention and 36.5% (n = 72/197) of control group women (p = 0.81). The total incidence of gestational diabetes diagnosed in the first or second half of pregnancy was 44.8% (107/239) in the intervention and 48.1% (111/231) in the control group (p = 0.48). Conclusions The high prevalence of impaired glucose metabolism was observed already in early pregnancy, which may have contributed to the lack of effect of the intervention.Peer reviewe