Biology subjects

Cremer, J.

Publications and source records attributed to Cremer, J..

5 recordsLinked to original sources

bioRxiv2022

Changing flows balance nutrient absorption and bacterial growth along the gut

Small intestine motility and its ensuing flow of luminal content impact both nutrient absorption and bacterial growth. To explore this interdependence we introduce a biophysical description of intestinal flow and absorption. Rooted in observations of mice we identify the average flow velocity as the key control of absorption efficiency and bacterial growth, independently of the exact contraction pattern. We uncover self-regulation of contraction and flow in response to nutrients and bacterial levels to promote efficient absorption while restraining detrimental bacterial overgrowth.

biophysics↗

bioRxiv2022

An Optimal Regulation of Fluxes Dictates Microbial Growth In and Out of Steady-State

Effective coordination of cellular processes is critical to ensure the competitive growth of microbial organisms. Pivotal to this coordination is the appropriate partitioning of cellular resources between protein synthesis via translation and the metabolism needed to sustain it. Here, we extend a low-dimensional allocation model to describe the dynamic control of this resource partitioning. At the core of this regulation is the optimal coordination of metabolic and translational fluxes, mechanistically achieved via the perception of charged- and uncharged-tRNA turnover. An extensive comparison with {approx} 60 data sets from Escherichia coli establishes this regulatory mechanisms biological veracity and demonstrates that a remarkably wide range of growth phenomena in and out of steady state can be predicted with quantitative accuracy. This predictive power, achieved with only a few biological parameters, cements the preeminent importance of optimal flux regulation across conditions and establishes low-dimensional allocation models as an ideal physiological framework to interrogate the dynamics of growth, competition, and adaptation in complex and ever-changing environments.

microbiology↗

bioRxiv2021

Coordination of gene expression with cell size enables Escherichia coli to efficiently maintain motility across conditions

To swim and navigate, motile bacteria synthesize a complex motility machinery involving flagella, motors, and a sensory system. A myriad of studies has elucidated the molecular processes involved, but less is known about the coordination of motility expression with cellular physiology: In Escherichia coli, motility genes are strongly upregulated in nutrient-poor conditions compared to nutrient-replete conditions; yet a quantitative link to cellular motility has not been developed. Here, we systematically investigate gene expression, swimming behavior, and cell growth across a broad spectrum of exponential growth condition. We establish that E. coli up-regulates the expression of motility genes at slow growth to compensate for reduction in cell size, such that the number of flagella per cell is maintained across conditions. The observed 4-5 flagella per cell is the minimum number needed to keep the majority of cells motile. This simple regulatory objective allows E. coli cells to remain motile across a broad range of growth conditions while keeping the biosynthetic and energetic demands to establish and drive the motility machinery at the minimum needed. Given the strong reduction in flagella synthesis resulting from cell size increases at fast growth, our findings also provide a novel physiological perspective on bacterial cell size control: A larger cell-size at fast growth is an efficient strategy to increase the allocation of cellular resources to the synthesis of those proteins required for fast growth, while maintaining processes such as motility which are only needed on a per-cell basis.

microbiology↗

bioRxiv2021

Suboptimal proteome allocation during changing environments constrains bacterial response and growth recovery

To sustain growth in fluctuating environments microbial organisms must respond appropriately. The response generally requires the synthesis of novel proteins, but this synthesis can be impeded due to the depletion of biosynthetic precursors when growth conditions vary. Microbes must thus devise effective response strategies to manage depleting precursors. To better understand these strategies, we here investigate the active response of Escherichia coli to changes in nutrient conditions, connecting transient gene-expression behavior to growth phenotypes. By synthetically modifying the gene expression during changing growth conditions, we show how the competition by genes for the limited protein synthesis capacity constrains the cellular response. Despite this constraint, cells substantially express genes that are not required, severely slowing down the response. These findings highlight that cells do not optimize growth and recovery in every encountered environment but rather exhibit hardwired response strategies that may have evolved to promote growth and fitness in their native environment and include the regulation of multiple genes. The constraint and the suboptimality of the cellular response uncovered in this study provides a conceptual framework relevant for many research applications, from the prediction of evolution and adaptation to the improvement of gene circuits in biotechnology.

microbiology↗

bioRxiv2020

Molecular epidemiology of mumps viruses detected in the Netherlands, 2017-2019

Mumps cases continue to occur, also in countries with a relatively high vaccination rate. The last major outbreaks of mumps in the Netherlands were from 2009-2012 and thereafter, only small clusters and single cases were reported. Molecular epidemiology can provide insights in the circulation of mumps viruses. The aims of the present study were to analyze the molecular epidemiology of mumps viruses in the Netherlands in 2017-2019 and to elucidate whether complete genome sequencing adds to the molecular resolution of mumps viruses when compared to sequencing of the mumps SH gene and non-coding regions (SH+NCRs). To this end, Sanger sequence data from the SH+NCRs were analyzed from 82 mumps genotype G viruses. In addition, the complete genomes were obtained from 10 mumps virus isolates using next-generation sequencing. Analysis of SH+NCRs of mumps viruses revealed the presence of two major lineages in the Netherlands, which was confirmed by analysis of complete genomes. Comparison of molecular resolution obtained with SH+NCRs and complete genomes clearly indicated that additional molecular resolution can be obtained by analyzing complete genomes. In conclusion, analysis of SH + NCRs sequence data from recent mumps genotype G viruses indicate that mumps viruses continue to circulate in the Netherlands and surrounding countries. However, to understand exact transmission trees and to compare mumps viruses on a large geographic scale, analysis of complete genomes is a very useful approach.

microbiology↗