The Microbacterium sp. C448 was isolated from a soil regularly exposed to sulfamethazine (SMZ), for its ability to partly mineralise this antibiotic and other related sulfonamides. The aim of our study was to explore its metabolic adaptation towards exposure to SMZ environmental (10 mg/L) and medicinal (250 mg/L) concentrations. Its transcriptomic and proteomic responses were analysed by focusing on the degradation regulon (sad genes) and resistance genes (folP and sul1). The transcriptomic and proteomic results were essentially congruent whatever the concentrations tested. In culture conditions, exposure to the highest concentration of SMZ led to the highest sad expression and Sad production, confirming these proteins’ role in sulfamethazine degradation in cellulo. Moreover, when sulfamethazine was completely degraded, Sad production tends to return to the basal level observed under control conditions. Congruence of transcriptomic and proteomic results was also observed for resistance genes. Although Dihydropteroate synthase (DHPS)-Sul1 protein was 100-fold more produced than that of DHPS-FolP, both were expressed at a basal level and were not affected by SMZ exposure. Moreover, non-targeted analyses showed overexpression and overproduction of a putative sulphate exporter W0Z8D9 in Microbacterium sp. C448 exposed to the highest SMZ concentration. In addition to sul1 resistance genes, this efflux pump could be involved in the sulfamethazine detoxification process by exporting the SO2 formed during its degradation. Acknowledgements : The authors thank the National Research Agency for its financial support (ANTIBIOTOX project ; Grant ANR-17-CE34-0003).