Deciphering the mechanisms of Carbapenem resistance propagation by studying conjugative Plasmid transfer – DeCa-P

In recent years, the global emergence of multi-drug resistant (MDR) bacteria has become a major public health problem and a priority for microbiology research. Resistance determinant are mainly carried by conjugative plasmids whose transfer from bacterial cell to cell accounts for 80% of acquired resistance. Investigating fundamental aspect of conjugation process to obtain informative knowledges is needed to find new ways to stop antimicrobial resistance (AMR) dissemination and prevent the emergence of new MDR bacteria. In DeCa-P project, we intend to focus on the understanding of AMR dissemination by studying the transfer mechanism of the pOXA-48a conjugative plasmid, encoding an OXA-family carbapenemase, which is at the origin of the dissemination of carbapenem resistance among Enterobacteriaceae due to its wide spread. Despite its rising incidence and the investigation of its molecular epidemiology, the pOXA-48a plasmid but also related IncL/M plasmids are poorly characterized.
The first objective of the DeCa-P project is to identify and characterize molecular determinants maintaining the pOXA-48a plasmid and driving its dissemination. The second objective intends to uncover the dynamics of pOXA-48a propagation at the plasmid level in vitro and evaluate the influence of environmental stress such as antibiotic treatment on pOXA-48a transfer dynamics.
This project includes multidisciplinary approaches to identify the genetic determinants of AMR transmission, understand its dynamic and its link with environmental factors, and model the emergence parameters of AMR.