NORESIST

Nocardiosis is an infection caused by environmental bacteria from the Nocardia genus. Nocardia are opportunistic pathogens and mainly infect immunocompromised patients or patients with underlying pathologies. The foci of infections are often found in the lungs as well as in the brain or on the skin. Nocardiosis is treated with a combination of several antibiotics administered over a long period. The most critical forms of nocardiosis (cerebral or systemic) are punctuated by treatment failures, and relapse and associated with a poor survival prognosis for patients. The difficulty of treating nocardiosis is notably linked to the differences in sensitivity to antibiotics from one strain of Nocardia to another. This is also partly due to that the antibiotic resistance mechanisms of Nocardia have been poorly explored so far. In this context, this research project aims to define the antibiotic sensitivity of the most frequently encountered strains of Nocardia in clinics. First, whole genome sequencing of clinical strains of Nocardia will enable to identification of a set of genes linked to drug resistance. A particular focus will be on the identification of beta-lactamases and N-acetyltransferases conferring resistance to penicillin derivatives and aminoglycosides respectively. Biochemical and structural approaches will be employed to confirm the function of the suspected proteins and the ability of the purified proteins to modify antibiotics will be tested. The expression profile of these genes Nocardia strains in parallel with the establishment of the antibiotic susceptibility profile will complement our bioinformatic and biochemical data. This project should provide fundamental knowledge in the poorly explored field of the antibiotic resistance of Nocardia. Additionally, our discoveries could have a direct and beneficial short-term impact on the treatment of Nocardiosis, in particular by guiding clinicians on proper antibiotic therapy to adapt to the clinical strain encountered