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The specific temporal evolution of bacterial and phage population sizes, in particular bacterial depletion and the emergence of a resistant bacterial population, can be seen as a kinetic fingerprint that depends on the manifold interactions of the specific phage–host pair during the course of infection. We have elaborated such a kinetic fingerprint for a human urinary tract Klebsiella pneumoniae isolate and its phage vB_KpnP_Lessing by a modeling approach based on data from in vitro co-culture. We found a faster depletion of the initially sensitive bacterial population than expected from simple mass action kinetics. A possible explanation for the rapid decline of the bacterial population is a synergistic interaction of phages which can be a favorable feature for phage therapies. In addition to this interaction characteristic, analysis of the kinetic fingerprint of this bacteria and phage combination revealed several relevant aspects of their population dynamics: A reduction of the bacterial concentration can be achieved only at high multiplicity of infection whereas bacterial extinction is hardly accomplished. Furthermore the binding affinity of the phage to bacteria is identified as one of the most crucial parameters for the reduction of the bacterial population size. Thus, kinetic fingerprinting can be used to infer phage–host interactions and to explore emergent dynamics which facilitates a rational design of phage therapies.
For a class of Cannings models we prove Haldane’s formula, π(sN)∼2sNρ2, for the fixation probability of a single beneficial mutant in the limit of large population size N and in the regime of moderately strong selection, i.e. for sN∼N−b and 0<b<1/2. Here, sN is the selective advantage of an individual carrying the beneficial type, and ρ2 is the (asymptotic) offspring variance. Our assumptions on the reproduction mechanism allow for a coupling of the beneficial allele’s frequency process with slightly supercritical Galton–Watson processes in the early phase of fixation.
We introduce a Cannings model with directional selection via a paintbox construction and establish a strong duality with the line counting process of a new Cannings ancestral selection graph in discrete time. This duality also yields a formula for the fixation probability of the beneficial type. Haldane’s formula states that for a single selectively advantageous individual in a population of haploid individuals of size N the probability of fixation is asymptotically (as N→∞) equal to the selective advantage of haploids sN divided by half of the offspring variance. For a class of offspring distributions within Kingman attraction we prove this asymptotics for sequences sN obeying N−1≪sN≪N−1/2, which is a regime of “moderately weak selection”. It turns out that for sN≪N−2/3 the Cannings ancestral selection graph is so close to the ancestral selection graph of a Moran model that a suitable coupling argument allows to play the problem back asymptotically to the fixation probability in the Moran model, which can be computed explicitly.