Search bioRxiv⌕ Search

Biology subjects

Geyrhofer, L.

Publications and source records attributed to Geyrhofer, L..

3 recordsLinked to original sources

Race to survival during antibiotic breakdown determines the minimal surviving population size

A common strategy used by bacteria to resist antibiotics is enzymatic degradation or modification. Such a collective mechanism also enhances the survival of nearby cells, an effect that increases with the number of bacteria that are present. Collective resistance is of clinical significance, yet a quantitative understanding at the population level is lacking. Here we develop a general theoretical framework of collective resistance under antibiotic degradation. Our modeling reveals that population survival crucially depends on the ratio of timescales of two processes: the rates of population death and antibiotic removal. However, it is insensitive to molecular, biological and kinetic details of the underlying processes that give rise to these timescales. Another important aspect for this race to survival is the degree of cooperativity, which is related to the permeability of the cell wall for antibiotics and enzymes. These observations motivate a coarse-grained, phenomenological model and simple experimental assay to measure the dose-dependent minimal surviving population size. From this model, two dimensionless parameters can be estimated, representing the populations race to survival and single-cell resistance. Our simple model may serve as reference for more complex situations, such as heterogeneous bacterial communities.

microbiology↗

Coexistence and cooperation in structured habitats

Many natural habitats are structured, which imposes certain environmental conditions on extant populations. Which conditions are important for coexistence of diverse communities, and how social traits in such populations stabilize, have been important ecological and evolutionary questions. We investigate a minimal ecological model of microbial population dynamics, that exhibits crucial features to show coexistence: Populations are repeatedly separated into compartmentalized habitats on a timescale typically longer than growth. In this framework, we consider several scenarios for possible interactions between different strains and their environments, which includes sharing a common nutrient source or expression of public goods that potentially increase population size. Examples for these public good dynamics are collective resistance against antibiotics, and enhanced iron-availability due to pyoverdine. We show that the two features of a long mixing timescale and spatial compartmentalization are already enough to enable coexisting strains. In the case of public goods, stable coexistence immediately entails cooperation.

evolutionary biology↗

CRISPR-based Herd Immunity Limits Phage Epidemics in Bacterial Populations

Pathogens are a driving force in evolution, giving rise to a diversity of host immune defenses. In order for a pathogen to spread in a population a sufficient number of its members must be susceptible to infection, as resistant individuals can prevent the spread of a pathogen among susceptible hosts in a process known as herd immunity. While herd immunity has been extensively studied in vertebrate populations, little is known about its role, if any, in the dynamics between bacteria and their phage pathogens. Here we explore the dynamics of T7 phage epidemics in structured and unstructured Escherichia coli populations consisting of differing mixtures of susceptible and resistant individuals harboring CRISPR immunity to the phage. Using both experiments and mathematical modelling we describe the conditions under which herd immunity arises in bacterial populations. Notably, the effects of herd immunity depend strongly on the presence of spatial structure in the population, the bacterial growth rate, and phage replication rate. The results of our model can apply to other host-pathogen systems to determine the herd immunity threshold from the relative speed of an epidemic wave in partially resistant populations. In addition, our findings suggest that herd immunity plays an important role in bacterial communities, as seen in other host-pathogen systems, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity.

evolutionary biology↗