A novel system of bacterial cell division arrest implicated in horizontal transmission of an integrative and conjugative element.

Integrative and conjugative elements (ICEs) are widespread mobile DNA elements in the prokaryotic world. ICEs are usually retained within the bacterial chromosome, but can be excised and transferred from a donor to a new recipient cell, even of another species. Horizontal transmission of ICEclc, a prevalent ICE in proteobacteria, only occurs from developed specialized transfer competent (tc) cells in the donor population. tc cells become entirely dedicated to the ICE transmission at the cost of cell proliferation. The cell growth impairment is mediated by two ICEclc located genes, parA and shi, but the mechanistic and dynamic details of this process are unknown. To better understand the function of ParA and Shi, we followed their intracellular behavior from fluorescent protein fusions, and studied host cell division at single-cell level. Superresolution imaging revealed that ParA-mCherry colocalized with the host nucleoid while Shi-GFP was enriched at the membrane during the growth impairment. Despite being enriched at different cellular locations, the two proteins showed in vivo interactions, and mutations in the Walker A motif of ParA dislocalized both ParA and Shi. In addition, ParA mutations in the ATPase motif abolished the growth arrest on the host cell. Time-lapse microscopy revealed that ParA and Shi initially delay cell division, suggesting an extension of the S phase of cells, but eventually completely inhibit cell elongation. The parA-shi locus is highly conserved in other ICEclc-related elements, and expressing ParA-Shi from ICEclc in other proteobacterial species caused similar growth arrest, suggesting that the system functions similarly across hosts. The results of our study provide mechanistic insight into the novel and unique system on ICEs and help to understand such epistatic interaction between ICE genes and host physiology that entails efficient horizontal gene transfer

Density-Dependent Recycling Promotes the Long-Term Survival of Bacterial Populations during Periods of Starvation

The amount of natural resources in the Earth’s environment is in flux, which can trigger catastrophic collapses of ecosystems. How populations survive under nutrient-poor conditions is a central question in ecology. Curiously, some bacteria persist for a long time in nutrient-poor environments. Although this survival may be accomplished through cell death and the recycling of dead cells, the importance of these processes and the mechanisms underlying the survival of the populations have not been quantitated. Here, we use microbial laboratory experiments and mathematical models to demonstrate that death and recycling are essential activities for the maintenance of cell survival. We also show that the behavior of the survivors is governed by population density feedback, wherein growth is limited not only by the available resources but also by the population density. The numerical simulations suggest that population density-dependent recycling could be an advantageous behavior under starvation conditions

The Architecture of Metabolic Networks Constrains the Evolution of Microbial Resource Hierarchies

Microbial strategies for resource use are an essential determinant of their fitness in complex habitats. When facing environments with multiple nutrients, microbes often use them sequentially according to a preference hierarchy, resulting in well-known patterns of diauxic growth. In theory, the evolutionary diversification of metabolic hierarchies could represent a mechanism supporting coexistence and biodiversity by enabling temporal segregation of niches. Despite this ecologically critical role, the extent to which substrate preference hierarchies can evolve and diversify remains largely unexplored. Here, we used genome-scale metabolic modeling to systematically explore the evolution of metabolic hierarchies across a vast space of metabolic network genotypes. We find that only a limited number of metabolic hierarchies can readily evolve, corresponding to the most commonly observed hierarchies in genome-derived models. We further show how the evolution of novel hierarchies is constrained by the architecture of central metabolism, which determines both the propensity to change ranks between pairs of substrates and the effect of specific reactions on hierarchy evolution. Our analysis sheds light on the genetic and mechanistic determinants of microbial metabolic hierarchies, opening new research avenues to understand their evolution, evolvability, and ecology. BT/Industriele Microbiologi

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study

Objectives To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan.Design Retrospective study.Setting Six hundred and thirty-one primary care institutions in Japan.Participants Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database.Primary and secondary outcome measures Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3–6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1–25 points).Results In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality.Conclusions The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era