Bacterial aggregation triggered by low-level antibiotic-mediated lysis.

Suspended bacterial aggregates play a central role in ocean biogeochemistry, industrial processes and probably many clinical infections - yet the factors that trigger aggregation remain poorly understood, as does the relationship between suspended aggregates and surface-attached biofilms. Here we show that very low doses of cell-wall targeting antibiotic, far below the minimal inhibitory concentration, can trigger aggregation of Escherichia coli cells. This occurs when a few cells lyse, releasing extracellular DNA - thus, cell-to-cell variability in antibiotic response leads to population-level aggregation.

Distinct types of multicellular aggregates in Pseudomonas aeruginosa liquid cultures.

Pseudomonas aeruginosa forms suspended multicellular aggregates when cultured in liquid media. These aggregates may be important in disease, and/or as a pathway to biofilm formation. The polysaccharide Psl and extracellular DNA (eDNA) have both been implicated in aggregation, but previous results depend strongly on the experimental conditions.

Active layer dynamics drives a transition to biofilm fingering.

The emergence of spatial organisation in biofilm growth is one of the most fundamental topics in biofilm biophysics and microbiology. It has long been known that growing biofilms can adopt smooth or rough interface morphologies, depending on the balance between nutrient supply and microbial growth; this 'fingering' transition has been linked with the average width of the 'active layer' of growing cells at the biofilm interface. Here we use long-time individual-based simulations of growing biofilms to investigate in detail the driving factors behind the biofilm-fingering transition.

Amplification Free Detection of SARS-CoV-2 Using Multi-Valent Binding.

We present the development of electrochemical impedance spectroscopy (EIS)-based biosensors for sensitive detection of SARS-CoV-2 RNA using multi-valent binding. By increasing the number of probe-target binding events per target molecule, multi-valent binding is a viable strategy for improving the biosensor performance. As EIS can provide sensitive and label-free measurements of nucleic acid targets during probe-target hybridization, we used multi-valent binding to build EIS biosensors for targeting SARS-CoV-2 RNA.

Model for Quorum-Sensing Mediated Stochastic Biofilm Nucleation.

Surface-attached bacterial biofilms cause disease and industrial biofouling, as well as being widespread in the natural environment. Density-dependent quorum sensing is one of the mechanisms implicated in biofilm initiation. Here we present and analyze a model for quorum-sensing triggered biofilm initiation.

Dynamic Diatom-Bacteria Consortia in Synthetic Plankton Communities.

Microalgae that form phytoplankton live and die in a complex microbial consortium in which they co-exist with bacteria and other microorganisms. The dynamics of species succession in the plankton depends on the interplay of these partners. Bacteria utilize substrates produced by the phototrophic algae, while algal growth can be supported by bacterial exudates.

A computational model for microbial colonization of an antifouling surface.

Biofouling of marine surfaces such as ship hulls is a major industrial problem. Antifouling (AF) paints delay the onset of biofouling by releasing biocidal chemicals. We present a computational model for microbial colonization of a biocide-releasing AF surface.

Lineage dynamics in growing biofilms: Spatial patterns of standing vs. diversity.

Microbial biofilms show high phenotypic and genetic diversity, yet the mechanisms underlying diversity generation and maintenance remain unclear. Here, we investigate how spatial patterns of growth activity within a biofilm lead to spatial patterns of genetic diversity. Using individual-based computer simulations, we show that the active layer of growing cells at the biofilm interface controls the distribution of lineages within the biofilm, and therefore the patterns of standing and diversity.

Tracking the stochastic growth of bacterial populations in microfluidic droplets.

Bacterial growth in microfluidic droplets is relevant in biotechnology, in microbial ecology, and in understanding stochastic population dynamics in small populations. However, it has proved challenging to automate measurement of absolute bacterial numbers within droplets, forcing the use of proxy measures for population size. Here we present a microfluidic device and imaging protocol that allows high-resolution imaging of thousands of droplets, such that individual bacteria stay in the focal plane and can be counted automatically.

Staff and patient perceptions of a community urinary catheter service.

Introduction: Urinary catheters are used extensively throughout healthcare for various reasons including management of urinary tract dysfunction. The purpose of this study was to simultaneously explore both catheter user experience and staff perception of catheter services within community urinary catheter care.

Methods: A questionnaire was conducted to investigate the views of community nursing staff.

Stability of β-lactam antibiotics in bacterial growth media.

Laboratory assays such as MIC tests assume that antibiotic molecules are stable in the chosen growth medium-but rapid degradation has been observed for antibiotics including β-lactams under some conditions in aqueous solution. Degradation rates in bacterial growth medium are less well known. Here, we develop a 'delay time bioassay' that provides a simple way to estimate antibiotic stability in bacterial growth media, using only a plate reader and without the need to measure the antibiotic concentration directly.

A Roadblock-and-Kill Mechanism of Action Model for the DNA-Targeting Antibiotic Ciprofloxacin.

Fluoroquinolones, antibiotics that cause DNA damage by inhibiting DNA topoisomerases, are clinically important, but their mechanism of action is not yet fully understood. In particular, the dynamical response of bacterial cells to fluoroquinolone exposure has hardly been investigated, although the SOS response, triggered by DNA damage, is often thought to play a key role. Here, we investigated the growth inhibition of the bacterium by the fluoroquinolone ciprofloxacin at low concentrations.

Phenotypic delay in the evolution of bacterial antibiotic resistance: Mechanistic models and their implications.

Phenotypic delay-the time delay between genetic mutation and expression of the corresponding phenotype-is generally neglected in evolutionary models, yet recent work suggests that it may be more common than previously assumed. Here, we use computer simulations and theory to investigate the significance of phenotypic delay for the evolution of bacterial resistance to antibiotics. We consider three mechanisms which could potentially cause phenotypic delay: effective polyploidy, dilution of antibiotic-sensitive molecules and accumulation of resistance-enhancing molecules.

Predictable properties of fitness landscapes induced by adaptational tradeoffs.

Fitness effects of mutations depend on environmental parameters. For example, mutations that increase fitness of bacteria at high antibiotic concentration often decrease fitness in the absence of antibiotic, exemplifying a tradeoff between adaptation to environmental extremes. We develop a mathematical model for fitness landscapes generated by such tradeoffs, based on experiments that determine the antibiotic dose-response curves of strains, and previous observations on antibiotic resistance mutations.

Computational design of probes to detect bacterial genomes by multivalent binding.

Rapid methods for diagnosis of bacterial infections are urgently needed to reduce inappropriate use of antibiotics, which contributes to antimicrobial resistance. In many rapid diagnostic methods, DNA oligonucleotide probes, attached to a surface, bind to specific nucleotide sequences in the DNA of a target pathogen. Typically, each probe binds to a single target sequence; i.

A simulation study of aggregation mediated by production of cohesive molecules.

Mechanical interactions between biological cells can be mediated by secreted products. Here, we investigate how such a scenario could affect the cells' collective behaviour. We show that if the concentration field of secreted products around a cell can be considered to be in steady state, this scenario can be mapped onto an effective attractive interaction that depends on the local cell density.

Growth-dependent drug susceptibility can prevent or enhance spatial expansion of a bacterial population.

As a population wave expands, organisms at the tip typically experience plentiful nutrients while those behind the front become nutrient-depleted. If the environment also contains a gradient of some inhibitor (e.g.

Bacterial growth: a statistical physicist's guide.

Bacterial growth presents many beautiful phenomena that pose new theoretical challenges to statistical physicists, and are also amenable to laboratory experimentation. This review provides some of the essential biological background, discusses recent applications of statistical physics in this field, and highlights the potential for future research.

Oxic-anoxic regime shifts mediated by feedbacks between biogeochemical processes and microbial community dynamics.

Although regime shifts are known from various ecosystems, the involvement of microbial communities is poorly understood. Here we show that gradual environmental changes induced by, for example, eutrophication or global warming can induce major oxic-anoxic regime shifts. We first investigate a mathematical model describing interactions between microbial communities and biogeochemical oxidation-reduction reactions.

Predicting the dynamics of bacterial growth inhibition by ribosome-targeting antibiotics.

Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance-yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time-dependent. Here, we use a theoretical model, previously applied to steady-state bacterial growth, to predict the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic.

Assembly of microbial communities in replicate nutrient-cycling model ecosystems follows divergent trajectories, leading to alternate stable states.

We studied in detail the reproducibility of community development in replicate nutrient-cycling microbial microcosms that were set up identically and allowed to develop under the same environmental conditions. Multiple replicate closed microcosms were constructed using pond sediment and water, enriched with cellulose and sulphate, and allowed to develop over several months under constant environmental conditions, after which their microbial communities were characterized using 16S rRNA gene sequencing. Our results show that initially similar microbial communities can follow alternative - yet stable - trajectories, diverging in time in a system size-dependent manner.

The PSL Polysaccharide Is a Social but Noncheatable Trait in Biofilms.

Extracellular polysaccharides are compounds secreted by microorganisms into the surrounding environment, and they are important for surface attachment and maintaining structural integrity within biofilms. The social nature of many extracellular polysaccharides remains unclear, and it has been suggested that they could function as either cooperative public goods or as traits that provide a competitive advantage. Here, we empirically tested the cooperative nature of the PSL polysaccharide, which is crucial for the formation of biofilms in We show that (i) PSL is not metabolically costly to produce; (ii) PSL provides population-level benefits in biofilms, for both growth and antibiotic tolerance; (iii) the benefits of PSL production are social and are shared with other cells; (iv) the benefits of PSL production appear to be preferentially directed toward cells which produce PSL; (v) cells which do not produce PSL are unable to successfully exploit cells which produce PSL.

Challenges in microbial ecology: building predictive understanding of community function and dynamics.

The importance of microbial communities (MCs) cannot be overstated. MCs underpin the biogeochemical cycles of the earth's soil, oceans and the atmosphere, and perform ecosystem functions that impact plants, animals and humans. Yet our ability to predict and manage the function of these highly complex, dynamically changing communities is limited.

Role of Multicellular Aggregates in Biofilm Formation.

Unlabelled: In traditional models ofin vitrobiofilm development, individual bacterial cells seed a surface, multiply, and mature into multicellular, three-dimensional structures. Much research has been devoted to elucidating the mechanisms governing the initial attachment of single cells to surfaces. However, in natural environments and during infection, bacterial cells tend to clump as multicellular aggregates, and biofilms can also slough off aggregates as a part of the dispersal process.