Biology subjects

Milstein, J.

Publications and source records attributed to Milstein, J..

4 recordsLinked to original sources

bioRxiv2026

The influence of cell morphology on the dynamics and stability of model bacterial communities

Understanding how structures arise in microbial communities remains an outstanding challenge in bacterial ecology. When replicating within dense and confined environments, bacterial populations may collectively self-organize as a result of mechanical interactions. Model dual-populations of bacteria, colonizing open-ended microchannels, were found to either quickly fixate to a single population or segregate into long-lived, coexisting populations. This latter quasi-stability results from the alignment of bacteria into lanes, forcing cells to grow toward the open ends of the channel, with inter-lane invasion events driving the boundary between populations. Here we apply agent-based (AB) simulations to explore the boundary dynamics between dual-bacterial populations of varying morphology and division rate. We find that the simulated boundary dynamics are well described by a simple drift-diffusion model, which enables us to estimate the mean time to fixation within competitive scenarios where the fixation time is difficult to access by AB simulations. Coccus cells display a competitive advantage over bacillus cells as they can more effectively invade and ultimately fixate, while coexisting populations of bacillus cells are effectively stable. And while faster-dividing cells should have a selective advantage, their morphologydetermines if this advantage drives fixation or acts as a defensive strategy to maintain their population. These findings highlight the critical role that cell morphology and mechanics play in shaping bacterial communities. Author summaryBacteria are often found in multi-species communities, many of which are critical to human health, the environment, and industry. Within these communities, a competition for resources shapes the overall population structure and resulting ecology. Model systems can provide a test bed for understanding the interaction networks of these more complex communities. Here we show how mechanical forces between cells and their environment can be critical to the stability (or instability) of a bacterial community. Using simulations of dual species competition within two-dimensional microchannels, along with mathematical modeling, we find that cell morphology can be a determining factor in the stability of a multi-species community.

biophysics↗

bioRxiv2023

Mechanics limit ecological diversity and promote heterogeneity in confined bacterial communities

Multi-species bacterial populations often inhabit confined and densely packed environments where spatial competition determines the ecological diversity of the community. However, the role of mechanical interactions in shaping the ecology is still poorly understood. Here we study a model system consisting of two populations of non-motile E. coli bacteria competing within open, monolayer micro-channels. The competitive dynamics is observed to be bi-phasic: after seeding, either one strain rapidly fixates or both strains orient into spatially stratified, stable communities. We find that mechanical interactions with other cells and local spatial constraints influence the resulting community ecology in unexpected ways, severely limiting the overall diversity of the communities while simultaneously allowing for the establishment of stable, heterogeneous populations of bacteria displaying disparate growth rates. Surprisingly, the populations have a high probability of coexisting even when one strain has a significant growth advantage. A more coccus morphology is shown to provide a selective advantage, but agent based simulations indicate this is due to hydrodynamic and adhesion effects within the microchannel and not from breaking of the nematic ordering. Our observations are qualitatively reproduced by a simple Polya urn model, which suggests the generality of our findings for confined population dynamics and highlights the importance of early colonization conditions on the resulting diversity and ecology of bacterial communities. These results provide fundamental insights into the determinants of community diversity in dense confined ecosystems where spatial exclusion is central to competition as in organized biofilms or intestinal crypts.

biophysics↗

bioRxiv2021

Highly potent photoinactivation of bacteria using a water soluble, cell permeable, DNA-binding photosensitizer

Antimicrobial photodynamic therapy (APDT) employs a photosensitizer, light, and molecular oxygen to treat infectious diseases via oxidative damage, with a low likelihood for the development of resistance. For optimal APDT efficacy, photosensitizers with cationic charges that can permeate bacteria cells and bind intracellular targets are desired to not limit oxidative damage to the outer bacterial structure. Here we report the application of brominated DAPI (Br-DAPI), a water-soluble, DNA-binding photosensitizer for eradication of both gram-negative and gram-positive bacteria (as demonstrated on N99 E. coli and B. subtilis, respectively). We observe intracellular uptake of Br-DAPI, ROS-mediated bacterial cell death via 1- and 2-photon excitation, and selective photocytotoxicity of bacteria over mammalian cells. Photocytotoxicity of both N99 E. coli and B. subtilis occurred at sub-micromolar concentrations (IC50 = 0.2 M - 0.4 M) and low light doses (5-minute irradiation times, 4.5 J cm-2 dose) making it superior to commonly employed APDT phenothiazinium photosensitizers such as methylene blue. Given its high potency and 2-photon excitability, Br-DAPI is a promising novel photosensitizer for in vivo APDT applications.

biophysics↗

bioRxiv2019

Growth Phase Dependent Chromosome Condensation and H-NS Protein Redistribution in E. coli Under Osmotic Stress

The heat-stable nucleoid-structuring (H-NS) protein is a global transcriptional regulator implicated in coordinating the expression of over 200 genes in E. coli bacteria. We have applied super-resolved microscopy to quantify the intracellular, spatial reorganization of H-NS in response to osmotic stress. We find that H-NS shows a growth phase dependent response to hyperosmotic shock. In stationary phase, H-NS detaches from a tightly compacted bacterial chromosome and is excluded from the nucleoid volume over an extended period of time. This behaviour is absent during rapid growth but may be induced by exposing the osmotically stressed culture to the DNA gyrase inhibitor, coumermycin. This compaction/H-NS exclusion phenomenon occurs in the presence of either potassium or sodium ions and is independent of the stress responsive sigma factor RpoS, or the H-NS paralog StpA.

microbiology↗