This project is aimed at revealling chemical and genetic basis of the mechanism for microbial degradation of azithromycin, a macrolide antibiotic which is widely used in human medicine to treat or prevent many bacterial infections. Microbial degradation of azithromycin represents one of the mechanisms for bacterial resistance to macrolide antibiotics. The work proposed here is focused on an activated sludge microbial community adapted to azithromycin and shown to have a key-role in its detoxification. The investigation includes the use of both culture-dependent and modern culture-independent approaches such as metagenomics and metatranscriptomics in combination with highly selective analytical methodology such as LC-MS/MS