Berlin 2024 – wissenschaftliches Programm
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DY: Fachverband Dynamik und Statistische Physik
DY 20: Statistical Physics of Biological Systems I (joint session DY/BP)
DY 20.3: Vortrag
Dienstag, 19. März 2024, 10:15–10:30, BH-N 334
Modelling antibiotic killing and tolerance dynamics in tuberculosis treatment — •Miriam Clincy1, Vijay Srinivasan2, Rosalind J Allen2, and Martin R Evans3 — 1Hochschule Esslingen, Esslingen, Germany — 2Friedrich-Schiller-Universität, Jena, Germany — 3University of Edinburgh, Edinburgh, UK
The bacterium Mycobacterium tuberculosis (Mtb), which causes tuberculosis, is the leading global cause of deaths from infectious disease. The antibiotic treatment regime for tuberculosis is very long, because Mtb can switch into tolerant physiological states that are only slowly killed by antibiotic. Here we introduce a stochastic two-species birth-death model for antibiotic treatment of an Mtb infection accounting for this switching.
Solving analytically for the probability generating function describing the treatment phase in which neither state proliferates allows 1) to recover the mean subpopulation dynamics from which numerical estimates for the birth, death and switching rates specifically for Mtb can be derived, and 2) the calculation of the extinction probability as a function of time. From the latter, a numerical measure for the extinction time of the bacterial population is defined. Studying this extinction time reveals distinct regimes in which the required treatment time is limited by either the rate of killing of tolerant bacteria, or the rate of switching out of the tolerant state.
Keywords: Stochastic Modelling; Phenotype Switching; Tuberculosis; Birth-Death Process