NlpI-mediated modulation of outer membrane vesicle production through peptidoglycan dynamics in Escherichia coli.

Outer membrane vesicles (OMVs) are ubiquitously secreted from the outer membrane (OM) of Gram-negative bacteria. These heterogeneous structures are composed of OM filled with periplasmic content from the site of budding. By analyzing mutants that have vesicle production phenotypes, we can gain insight into the mechanism of OMV budding in wild-type cells, which has thus far remained elusive. In this study, we present data demonstrating that the hypervesiculation phenotype of the nlpI deletion mutant of Escherichia coli correlates with changes in peptidoglycan (PG) dynamics. Our data indicate that in stationary phase cultures the nlpI mutant exhibits increased PG synthesis that is dependent on spr, consistent with a model in which NlpI controls the activity of the PG endopeptidase Spr. In log phase, the nlpI mutation was suppressed by a dacB mutation, suggesting that NlpI regulates penicillin-binding protein 4 (PBP4) during exponential growth. The data support a model in which NlpI negatively regulates PBP4 activity during log phase, and Spr activity during stationary phase, and that in the absence of NlpI, the cell survives by increasing PG synthesis. Further, the nlpI mutant exhibited a significant decrease in covalent outer membrane (OM-PG) envelope stabilizing cross-links, consistent with its high level of OMV production. Based on these results, we propose that one mechanism wild-type Gram-negative bacteria can use to modulate vesiculation is by altering PG-OM cross-linking via localized modulation of PG degradation and synthesis.

Differential developmental trajectories of magnetic susceptibility in human brain gray and white matter over the lifespan

As indicated by several recent studies, magnetic susceptibility of the brain is influenced mainly by myelin in the white matter and by iron deposits in the deep nuclei. Myelination and iron deposition in the brain evolve both spatially and temporally. This evolution reflects an important characteristic of normal brain development and ageing. In this study, we assessed the changes of regional susceptibility in the human brain in vivo by examining the developmental and ageing process from 1 to 83 years of age. The evolution of magnetic susceptibility over this lifespan was found to display differential trajectories between the gray and the white matter. In both cortical and subcortical white matter, an initial decrease followed by a subsequent increase in magnetic susceptibility was observed, which could be fitted by a Poisson curve. In the gray matter, including the cortical gray matter and the iron-rich deep nuclei, magnetic susceptibility displayed a monotonic increase that can be described by an exponential growth. The rate of change varied according to functional and anatomical regions of the brain. For the brain nuclei, the age-related changes of susceptibility were in good agreement with the findings from R2* measurement. Our results suggest that magnetic susceptibility may provide valuable information regarding the spatial and temporal patterns of brain myelination and iron deposition during brain maturation and ageing. © 2013 Wiley Periodicals, Inc.