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Insights from within-host dynamics on the coexistence of antibiotic resistant and sensitive pathogens

Descripción del proyecto

Modelización de la evolución de la resistencia bacteriana a los antibióticos

La resistencia bacteriana a los antibióticos supone un enorme problema de salud pública. La coexistencia de genotipos sensibles y resistentes a los antibióticos en una misma población es un problema sin resolver. Los modelos epidemiológicos actuales solo predicen la dominancia de una de las dos cepas o adolecen de generalización. El proyecto financiado con fondos europeos PolyPath tiene como objetivo resolver estos problemas asociando la dinámica de los patógenos dentro del huésped con la transmisión entre huéspedes de las bacterias. La modelización del sistema de dentro del huésped permitirá predecir la tasa de aparición de resistencia y la abundancia de bacterias sensibles y resistentes con tratamiento antibiótico y sin dicho tratamiento. Las bacterias resistentes prosperan con tratamiento antibiótico, mientras que la cepa sensible tiene ventaja a la hora de invadir y colonizar huéspedes no tratados. El proyecto ayudará a identificar las estrategias de tratamiento óptimas para resolver la resistencia a los antibióticos.

Objetivo

Understanding and controlling the evolution of antibiotic resistant strains is one of the biggest public health challenges of our time. Despite a vast amount of data gathered and models being developed, coexistence of antibiotic resistant and sensitive genotypes within the same bacterial pathogen is still an unresolved problem. Simple epidemiological models predict the dominance of either of the two strains while more complex models suffer from generality. Using empirical evidence, I set out to resolve this problem by coupling within-host pathogen dynamics and between-host transmission of bacteria. First, stochastically modelling the within-host system I will develop predictions for the rate of resistance emergence and abundance of sensitive and resistant individuals in hosts with or without antibiotic treatment. While resistant bacteria thrive under antibiotic treatment, the sensitive strain has an advantage in invading and colonising untreated hosts. The outcomes help to get a more detailed understanding of the within-host dynamics, e.g. identification of optimal treatment strategies to confine the evolution of antibiotic resistance. Feeding these results into the dynamics on the population level, the between-host level, will result in a within-between-host feedback. Fitting and confronting the model to empirical data on prevalence and resistance emergence in Streptococcus pneuomoniae and Escherichia coli will conclude this project. The mechanistic implementation of the dynamics can immediately be linked to data which is of great importance given the increasing amount of empirical studies in the field of epidemiology. Through the theoretical and applied results, the study will add new insights and predictions in the field of infectious disease evolution and be able to identify factors enabling the stable coexistence of antibiotic resistant and sensitive bacteria.

Palabras clave

Coordinador

SORBONNE UNIVERSITE
Aportación neta de la UEn
€ 184 707,84
Dirección
21 RUE DE L'ECOLE DE MEDECINE
75006 Paris
Francia

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Región
Ile-de-France Ile-de-France Paris
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 184 707,84