Understanding The Role Of Plasmid Ecology In The Coevolution Of Virulence And Antimicrobial Resistance In Klebsiella Pneumoniae

Funder
John Fell Fund

Principal Investigators
Dr Marc Choisy
Dr Pham Thanh Duy

Duration
April 2022 – December 2023

This project aims to develop mathematical models to understand and predict the evolutionary dynamics of MDR, hv and MDR+hv, and the role of plasmid transmission in that.

Background

Klebsiella pneumoniae (Kp) causes severe infections in the hospital setting, where they are often associated with antimicrobial multidrug resistance (MDR), rendering their treatment challenging. In recent decades, plasmid-mediated hypervirulent (hv) variants have emerged in the community across Southeast Asia. More recently, convergent MDR+hv variants emerged, posing a global public health threat. This project aims to understand the evolutionary dynamics of MDR, hv and MDR+hv.

Aims

We will develop mathematical models to understand and predict the evolutionary dynamics of MDR, hv and MDR+hv, and the role of plasmid transmission in that. Competition experiments will be conducted in the lab to characterize the fitness of MDR, hv and MDR+hv in various environmental conditions (antimicrobials and other stresses) and calibrate the mathematical models. The models will be used to predict epidemiological trends in the community and the hospital settings. These predictions will be confronted with actual data from the Hospital for Tropical Diseases in Ho Chi Minh City, Viet Nam.

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